SLC9A6 (Sodium/hydrogen exchanger 6) variants and mutations
SLC9A6 (also known as Sodium/hydrogen exchanger 6) is a human protein-coding gene encoding a sodium/hydrogen exchanger 6 protein. It regulates endosomal pH and trafficking in neurons and other cells by exchanging luminal protons for cytosolic sodium or potassium. Loss-of-function variants cause Christianson syndrome, with severe developmental impairment, absent speech, epilepsy, ataxia, and acquired microcephaly. This analysis covers 351 SLC9A6 variants and mutations. Of these, 87% have computational variant effect predictions. Disease context includes Christianson syndrome, Intellectual disability, and hereditary disease. Example SLC9A6 variants include M1K, M1R, and M1V.
Variant analysis overview
- Gene: SLC9A6
- Protein: Sodium/hydrogen exchanger 6
- UniProt accession: Q92581
- Organism: Homo sapiens
- Variants analyzed: 351
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 75 unspecified-consequence records; 192 missense variants; 61 synonymous variants; 5 stop-gained variants; 12 frameshift variants; 3 in-frame deletions; 1 in-frame insertions; 1 splice-region variants; 1 substitution
- Prediction scores: 307 variants have prediction scores (87% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Christianson syndrome, Intellectual disability, hereditary disease, microcephaly, Angelman syndrome, neurodegenerative disease, Seizure, Global developmental delay, Sleep disturbance, Recurrent respiratory infections, scoliosis, Gastrostomy tube feeding in infancy.
Protein structure and variant hotspots
- Protein features: 12 transmembrane segments; 1 post-translational modification sites.
- Structural context: 68 variants have structural context.
- PTM context: 5 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable SLC9A6 variants
Examples include M1K, M1R, M1V, A2V, A2D, R3R, R3G, R3W. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1K (p.Met1Lys), rs1006154022, ClinGen CA414606321, ClinVar RCV001567241, MetaLR 0.15, MetaSVM -0.96, Uncertain significance, not provided
- M1R (p.Met1Arg), rs1006154022, ClinGen CA16608696, ClinVar RCV000433846, ClinVar RCV001507050, MetaLR 0.15, MetaSVM -0.96, Uncertain significance, Christianson syndrome
- M1V (p.Met1Val), rs782640388, ClinGen CA414606320, ClinVar RCV001058825, ClinVar RCV001374987, MetaLR 0.12, MetaSVM -1.02, Uncertain significance, not provided; Christianson syndrome; Neurodevelopmental disorder
- A2V (p.Ala2Val), rs1334602422, gnomAD X-135985507-C-T, CADD 22.60
- A2D (p.Ala2Asp), gnomAD X-135985507-C-A, CADD 22.70
- R3R (p.Arg3Arg), gnomAD X-135985509-C-A, CADD 13.00
- R3G (p.Arg3Gly), rs1556614701, gnomAD X-135985509-C-G, CADD 21.40
- R3W (p.Arg3Trp), rs1556614701, gnomAD X-135985509-C-T, CADD 22.80
- R3Q (p.Arg3Gln), gnomAD X-135985510-G-A, CADD 19.80
- R3L (p.Arg3Leu), rs1016216648, gnomAD X-135985510-G-T, CADD 15.60
- R3P (p.Arg3Pro), gnomAD X-135985510-G-C, CADD 19.90
- R4S (p.Arg4Ser), rs2089317936, gnomAD X-135985512-C-A, CADD 18.00
- R4C (p.Arg4Cys), gnomAD X-135985512-C-T, CADD 23.10
- R4R (p.Arg4Arg), rs1415889484, gnomAD X-135985514-C-G, CADD 13.70
- G5C (p.Gly5Cys), gnomAD X-135985515-G-T, CADD 11.90
- G5S (p.Gly5Ser), rs895044278, gnomAD X-135985515-G-A, CADD 12.90
- G5D (p.Gly5Asp), gnomAD X-135985516-G-A, CADD 20.50
- G5V (p.Gly5Val), gnomAD X-135985516-G-T, CADD 19.90
- G5G (p.Gly5Gly), gnomAD X-135985517-C-A, CADD 12.60
- W6R (p.Trp6Arg), rs2521062188, ClinGen CA414606348, ClinVar RCV003319789, ClinVar RCV005102887, CADD 21.50, Uncertain significance, not provided; Christianson syndrome
- W6* (p.Trp6Ter), gnomAD X-135985519-G-A, CADD 35.00
- W6L (p.Trp6Leu), gnomAD X-135985519-G-T, CADD 19.40
- W6C (p.Trp6Cys), rs1012532789, gnomAD X-135985520-G-C, CADD 22.30
- R7W (p.Arg7Trp), gnomAD X-135985521-C-T, CADD 23.50
- R7R (p.Arg7Arg), gnomAD X-135985521-C-A, CADD 13.10
- R7Q (p.Arg7Gln), rs781845340, gnomAD X-135985522-G-A, CADD 22.00
- R8W (p.Arg8Trp), gnomAD X-135985524-C-T, CADD 23.00
- R8L (p.Arg8Leu), rs782480145, gnomAD X-135985525-G-T, CADD 18.80
- R8R (p.Arg8Arg), rs1556614713, gnomAD X-135985526-G-T, CADD 10.40
- A9S (p.Ala9Ser), rs201523857, ClinGen CA414606364, ClinVar RCV001331523, UniProt VAR 087516, CADD 13.00, Benign, Christianson syndrome
- A9P (p.Ala9Pro), rs201523857, gnomAD X-135985527-G-C, CADD 15.80
- A9T (p.Ala9Thr), gnomAD X-135985527-G-A, CADD 14.30
- A9E (p.Ala9Glu), gnomAD X-135985528-C-A, CADD 3.15
- A9V (p.Ala9Val), gnomAD X-135985528-C-T, CADD 8.15
- P10L (p.Pro10Leu), rs1181161585, gnomAD X-135985531-C-T, CADD 18.00
- P10P (p.Pro10Pro), gnomAD X-135985532-C-A, CADD 7.55
- L11F (p.Leu11Phe), rs971227843, gnomAD X-135985533-C-T, CADD 7.60
- L11H (p.Leu11His), gnomAD X-135985534-T-A, CADD 14.60
- L11L (p.Leu11Leu), gnomAD X-135985535-C-A, CADD 6.25
- R12S (p.Arg12Ser), rs1237626837, gnomAD X-135985536-C-A, CADD 11.90
- R12L (p.Arg12Leu), gnomAD X-135985537-G-T, CADD 9.33
- R13C (p.Arg13Cys), rs1556614725, ClinGen CA414606387, NCI-TCGA Cosmic COSV1008, cosmic curated COSV10085, AlphaMissense 0.34, MetaLR 0.09, Likely benign, Christianson syndrome
- R13S (p.Arg13Ser), gnomAD X-135985539-C-A, CADD 12.70
- R13H (p.Arg13His), rs186203433, gnomAD X-135985540-G-A, CADD 15.50
- R13L (p.Arg13Leu), gnomAD X-135985540-G-T, CADD 15.00
- G14V (p.Gly14Val), gnomAD X-135985543-G-T, CADD 19.30
- G14G (p.Gly14Gly), gnomAD X-135985544-C-A, CADD 7.41
- V15F (p.Val15Phe), gnomAD X-135985545-G-T, CADD 14.00
- V15G (p.Val15Gly), gnomAD X-135985546-T-G, CADD 7.85
- V15D (p.Val15Asp), rs2089319510, gnomAD X-135985546-T-A, CADD 8.91
- V15E (p.Val15Glu), rs1556614805, gnomAD X-135985675-T-A, CADD 15.20
- G16R (p.Gly16Arg), rs2089319617, ClinGen CA414606403, ClinVar RCV003513405, AlphaMissense 0.11, MetaLR 0.12, Uncertain significance, Christianson syndrome
- G16V (p.Gly16Val), rs1556614730, gnomAD X-135985549-G-T, CADD 14.10
- G16G (p.Gly16Gly), gnomAD X-135985550-C-T, CADD 7.95
- S17H (p.Ser17His), rs1157995682, gnomAD X-135985527-G-GCA, CADD 22.60
- S17N (p.Ser17Asn), gnomAD X-135985552-G-A, CADD 1.24
- S17I (p.Ser17Ile), gnomAD X-135985552-G-T, CADD 7.05
- S17S (p.Ser17Ser), gnomAD X-135985553-C-T, CADD 7.48
- S17A (p.Ser17Ala), gnomAD X-135985677-T-G, CADD 16.10, PolyPhen-2 0.16
- S17Y (p.Ser17Tyr), gnomAD X-135985678-C-A, CADD 23.90, PolyPhen-2 0.73
- S18I (p.Ser18Ile), gnomAD X-135985555-G-T, CADD 8.55
- S18S (p.Ser18Ser), rs781963863, gnomAD X-135985715-C-T, CADD 11.10
- P19S (p.Pro19Ser), gnomAD X-135985557-C-T, CADD 6.09
- P19L (p.Pro19Leu), rs2089319734, gnomAD X-135985558-C-T, CADD 10.50
- P19P (p.Pro19Pro), gnomAD X-135985559-C-G, CADD 8.09
- R20E (p.Arg20Glu), gnomAD X-135985556-TC-T, CADD 16.40
- R20* (p.Arg20Ter), rs1556614733, gnomAD X-135985560-C-T, CADD 26.90
- R20G (p.Arg20Gly), rs1556614733, gnomAD X-135985560-C-G, CADD 9.94
- R20R (p.Arg20Arg), gnomAD X-135985560-C-A, CADD 7.94
- R20L (p.Arg20Leu), gnomAD X-135985561-G-T, CADD 15.10
- R20Q (p.Arg20Gln), gnomAD X-135985561-G-A, CADD 14.70
- A21P (p.Ala21Pro), rs1556614734, gnomAD X-135985563-G-C, CADD 9.77
- A21S (p.Ala21Ser), rs1556614734, gnomAD X-135985563-G-T, CADD 6.61
- A21V (p.Ala21Val), gnomAD X-135985564-C-T, CADD 8.62
- A21A (p.Ala21Ala), rs1556614735, gnomAD X-135985565-C-A, CADD 7.00
- R22C (p.Arg22Cys), rs782282515, gnomAD X-135985566-C-T, CADD 17.00
- R22H (p.Arg22His), rs2089320091, gnomAD X-135985567-G-A, CADD 13.70
- R22P (p.Arg22Pro), rs2089320091, gnomAD X-135985567-G-C, CADD 12.60
- R22L (p.Arg22Leu), gnomAD X-135985567-G-T, CADD 12.00
- R22R (p.Arg22Arg), rs1282592417, gnomAD X-135985568-C-G, CADD 7.42
- R23G (p.Arg23Gly), rs796053277, gnomAD X-135985569-A-G, CADD 6.52
- R23R (p.Arg23Arg), rs2148129449, gnomAD X-135985571-G-A, CADD 8.37
- L24F (p.Leu24Phe), rs2148129457, ClinGen CA414606454, ClinVar RCV001975690, ClinVar RCV003128838, CADD 6.58, Uncertain significance, not provided; Christianson syndrome
- L24I (p.Leu24Ile), gnomAD X-135985572-C-A, CADD 8.36
- L24P (p.Leu24Pro), gnomAD X-135985573-T-C, CADD 16.80
- L24L (p.Leu24Leu), rs1556614739, gnomAD X-135985574-C-T, CADD 6.08
- L24V (p.Leu24Val), rs796053296, gnomAD X-135985722-C-G, CADD 22.40, PolyPhen-2 0.91
- M25L (p.Met25Leu), rs797044619, gnomAD X-135985575-A-C, CADD 6.64
- p.Arg26 Pro27del, gnomAD X-135985577-GCGGC, CADD 12.50
- R26R (p.Arg26Arg), gnomAD X-135985578-C-A, CADD 8.79
- R26W (p.Arg26Trp), gnomAD X-135985578-C-T, CADD 22.50
- R26G (p.Arg26Gly), rs782396686, gnomAD X-135985578-C-G, CADD 13.00
- R26L (p.Arg26Leu), gnomAD X-135985579-G-T, CADD 14.30
- R26Q (p.Arg26Gln), gnomAD X-135985579-G-A, CADD 14.50
- P27S (p.Pro27Ser), rs782655120, gnomAD X-135985581-C-T, CADD 8.88
- P27R (p.Pro27Arg), gnomAD X-135985582-C-G, CADD 9.84
- P27H (p.Pro27His), rs782242879, gnomAD X-135985582-C-A, CADD 12.80
- P27P (p.Pro27Pro), rs371561021, gnomAD X-135985583-C-T, CADD 7.92
- P27A (p.Pro27Ala), gnomAD X-135994827-C-G, CADD 17.40, PolyPhen-2 0.14
- P27L (p.Pro27Leu), rs782469016, gnomAD X-135994828-C-T, AlphaMissense 0.20, MetaLR 0.03
- L28F (p.Leu28Phe), rs781947192, gnomAD X-135985584-C-T, CADD 6.02
- L28L (p.Leu28Leu), rs2089324822, gnomAD X-135985739-G-A, CADD 10.40
- p.Trp29 Ala33delinsSer, gnomAD X-135985587-TGGTT, CADD 15.80
- W29L (p.Trp29Leu), gnomAD X-135985588-G-T, CADD 18.50
- W29* (p.Trp29Ter), rs2089320841, gnomAD X-135985588-G-A, CADD 34.00
- L31V (p.Leu31Val), rs782123546, gnomAD X-135985749-C-G, CADD 20.60, PolyPhen-2 0.65
- L31L (p.Leu31Leu), rs370054765, gnomAD X-135985751-C-T, CADD 12.40
- L32I (p.Leu32Ile), rs2521064023, ClinGen CA414606501, ClinVar RCV002630898, ClinVar RCV005928313, Likely benign, Christianson syndrome
- L32L (p.Leu32Leu), rs1556614844, gnomAD X-135985772-C-T, CADD 12.10
- A33S (p.Ala33Ser), rs782312727, gnomAD X-135985599-G-T, CADD 13.30
- A33T (p.Ala33Thr), rs782312727, gnomAD X-135985599-G-A, CADD 14.90
- A33E (p.Ala33Glu), gnomAD X-135985600-C-A, CADD 14.70
- V34E (p.Val34Glu), gnomAD X-135985602-GTGGG, CADD 24.70
- G35S (p.Gly35Ser), rs781943101, gnomAD X-135985605-G-A, CADD 13.90
- G35A (p.Gly35Ala), rs1382310975, gnomAD X-135985606-G-C, CADD 17.10
- V36I (p.Val36Ile), rs2089321131, ClinGen CA414606524, ClinVar RCV002413149, AlphaMissense 0.07, MetaLR 0.07, Uncertain significance, Inborn genetic diseases
- F37S (p.Phe37Ser), rs1556614753, gnomAD X-135985612-T-C, CADD 17.70
- F37F (p.Phe37Phe), rs977361236, gnomAD X-135985733-C-T, CADD 12.50
- D38N (p.Asp38Asn), gnomAD X-135985614-G-A, CADD 15.90
- D38E (p.Asp38Glu), rs1556614794, gnomAD X-135985664-C-G, CADD 11.40, PolyPhen-2 0.01
- A40T (p.Ala40Thr), gnomAD X-135985620-G-A, CADD 16.50
- A40S (p.Ala40Ser), gnomAD X-135985620-G-T, CADD 15.20
- A40E (p.Ala40Glu), rs2089321337, gnomAD X-135985620-GC-G, CADD 24.70
- G41A (p.Gly41Ala), gnomAD X-135985623-GGGGC, CADD 24.10
- G41E (p.Gly41Glu), rs782774568, gnomAD X-135985624-G-A, CADD 22.90
- A42G (p.Ala42Gly), rs781993737, gnomAD X-135985627-C-G, CADD 21.30
- D44N (p.Asp44Asn), rs2521064691, ClinGen CA414606575, ClinVar RCV003325869, Uncertain significance, not provided
- D44E (p.Asp44Glu), rs1343262050, gnomAD X-135985634-C-A, CADD 12.00
- D44D (p.Asp44Asp), rs1343262050, gnomAD X-135985634-C-T, CADD 8.88
- G45D (p.Gly45Asp), rs2521064844, ClinGen CA414606586, ClinVar RCV003513269, Uncertain significance, Christianson syndrome
- G45C (p.Gly45Cys), rs1556614763, gnomAD X-135985635-G-T, CADD 20.20
- G46D (p.Gly46Asp), rs782736274, gnomAD X-135985639-G-A, CADD 9.79
- G46G (p.Gly46Gly), rs1030979223, gnomAD X-135985640-C-A, CADD 3.06
- G47G (p.Gly47Gly), rs139299794, gnomAD X-135985643-C-T, CADD 8.16
- G48del (p.Gly48del), gnomAD X-135985633-ACGG-, CADD 13.40
- p.Gly48dup, rs796053292, gnomAD X-135985633-A-ACG, CADD 16.20
- G48R (p.Gly48Arg), rs782537893, gnomAD X-135985644-G-C, CADD 5.21
- G48G (p.Gly48Gly), rs781790298, gnomAD X-135985811-C-T, CADD 14.30
- G48C (p.Gly48Cys), gnomAD X-135985827-G-T, CADD 34.00, PolyPhen-2 1.00
- E49K (p.Glu49Lys), rs2089322133, gnomAD X-135985647-G-A, CADD 15.30
- E49Q (p.Glu49Gln), gnomAD X-135985665-G-C, CADD 22.70, PolyPhen-2 0.83
- E49G (p.Glu49Gly), rs782569149, gnomAD X-135985669-A-G, CADD 22.20, PolyPhen-2 0.77
- E49D (p.Glu49Asp), gnomAD X-135985694-G-C, CADD 14.60, PolyPhen-2 0.95
- E49E (p.Glu49Glu), rs2089323511, gnomAD X-135985697-G-A, CADD 7.48
- A50S (p.Ala50Ser), rs367724979, ClinGen CA318535, ClinVar RCV000865182, ClinVar RCV001721224, CADD 6.61, Likely benign, Christianson syndrome
- A50V (p.Ala50Val), rs1161139035, gnomAD X-135985651-C-T, CADD 12.90
- R51K (p.Arg51Lys), rs782509280, gnomAD X-135985654-G-A, CADD 16.40
- R51R (p.Arg51Arg), rs782090744, gnomAD X-135985655-A-G, CADD 13.80
- R51C (p.Arg51Cys), gnomAD X-135985782-C-T, CADD 25.20, PolyPhen-2 0.38
- R51G (p.Arg51Gly), gnomAD X-135985791-C-G, CADD 26.20, PolyPhen-2 0.91
- A52T (p.Ala52Thr), rs782214077, gnomAD X-135985656-G-A, CADD 21.20
- A52A (p.Ala52Ala), rs911499882, gnomAD X-135985658-C-T, CADD 11.00
- M53V (p.Met53Val), gnomAD X-135985818-A-G, CADD 22.20, PolyPhen-2 0.40
- I57V (p.Ile57Val), gnomAD X-135985728-A-G, CADD 14.50, PolyPhen-2 0.01
- I57I (p.Ile57Ile), gnomAD X-135985730-C-T, CADD 12.40
- I57L (p.Ile57Leu), rs1342307092, gnomAD X-135985764-A-C, CADD 26.20, PolyPhen-2 0.09
- V58M (p.Val58Met), rs906567942, gnomAD X-135994794-G-A, CADD 22.60, PolyPhen-2 0.43
- V58L (p.Val58Leu), gnomAD X-135994803-G-T, CADD 20.40, PolyPhen-2 0.02
- V58I (p.Val58Ile), rs1315183165, gnomAD X-135994824-G-A, AlphaMissense 0.07, MetaLR 0.03
- V58V (p.Val58Val), gnomAD X-135994847-G-A, CADD 8.76
- K61R (p.Lys61Arg), rs1556614847, gnomAD X-135985777-A-G, CADD 28.80, PolyPhen-2 0.94
- K61K (p.Lys61Lys), rs1301281396, gnomAD X-135985778-G-A, CADD 14.70
- Q62R (p.Gln62Arg), gnomAD X-135985708-A-G, CADD 23.10, PolyPhen-2 0.19
- H67H (p.His67His), rs1603185062, gnomAD X-135985781-C-T, CADD 13.20
- H67R (p.His67Arg), rs1060502675, gnomAD X-135994822-A-G, CADD 16.70, PolyPhen-2 0.10
- R68W (p.Arg68Trp), rs782767811, gnomAD X-135994809-C-T, CADD 28.60, PolyPhen-2 0.98
- R68Q (p.Arg68Gln), rs781844274, gnomAD X-135994810-G-A, CADD 27.60, PolyPhen-2 0.92
- Q69R (p.Gln69Arg), rs1406781654, gnomAD X-135994867-A-G, CADD 17.70, PolyPhen-2 0.00
- S71G (p.Ser71Gly), rs2089324047, ClinGen CA414606761, ClinVar RCV002283328, AlphaMissense 0.98, MetaLR 0.32, Conflicting interpretations, not provided; Christianson syndrome
- S71T (p.Ser71Thr), rs1556616246, gnomAD X-135994831-G-C, CADD 18.80, PolyPhen-2 0.17
- S71S (p.Ser71Ser), gnomAD X-135994832-T-C, CADD 2.55
- S71R (p.Ser71Arg), gnomAD X-135994856-C-G, CADD 22.70, PolyPhen-2 0.65
- N73N (p.Asn73Asn), gnomAD X-135994841-T-C, CADD 8.61
- N73D (p.Asn73Asp), gnomAD X-135994893-A-G, CADD 22.80, PolyPhen-2 0.28
- L74F (p.Leu74Phe), rs1556616215, gnomAD X-135994793-G-C, CADD 21.80, PolyPhen-2 0.05
- L74P (p.Leu74Pro), gnomAD X-135994801-T-C, CADD 26.60, PolyPhen-2 0.67
- L74L (p.Leu74Leu), rs1264299738, gnomAD X-135994802-T-C, CADD 8.76
- T82T (p.Thr82Thr), gnomAD X-135985754-C-T, CADD 11.90
- T82A (p.Thr82Ala), rs2148129982, gnomAD X-135985761-A-G, CADD 23.70, PolyPhen-2 0.24
- T82P (p.Thr82Pro), gnomAD X-135985761-A-C, CADD 26.40, PolyPhen-2 0.97
Public SLC9A6 analysis runs
- SLC9A6 analysis run — SLC9A6 (351 variants) — completed 2026-08-20