Retinal disorder: genes and variants

Genes linked to Retinal disorder

• ABCA4: Retinal-specific phospholipid-transporting ATPase ABCA4

  It flips retinal-derived lipid adducts across photoreceptor disc membranes so they can be cleared during the visual cycle. Biallelic loss-of-function variants cause Stargardt disease and can also produce cone-rod dystrophy or retinitis pigmentosa.

  7 disease-causing and 5 uncertain variants in ABCA4 are linked to Retinal disorder.

• BEST1: Bestrophin-1

  It helps regulate ion transport and fluid homeostasis across the retinal pigment epithelium. Pathogenic variants cause bestrophinopathies including Best vitelliform macular dystrophy, autosomal recessive bestrophinopathy, and some retinitis pigmentosa phenotypes.

  4 disease-causing and 0 uncertain variants in BEST1 are linked to Retinal disorder.

• RHO: Rhodopsin

  Photon absorption converts its retinal chromophore and triggers the G-protein cascade that initiates rod phototransduction. Pathogenic variants are a major cause of autosomal dominant retinitis pigmentosa and can also cause congenital stationary night blindness.

  3 disease-causing and 1 uncertain variants in RHO are linked to Retinal disorder.

• PRPH2: Peripherin-2

  It organizes and stabilizes the rim structure of photoreceptor outer-segment discs. Pathogenic variants cause a wide range of inherited retinal diseases including retinitis pigmentosa, pattern dystrophy, and macular dystrophy.

  0 disease-causing and 2 uncertain variants in PRPH2 are linked to Retinal disorder.

• USH2A: Usherin

  It helps organize extracellular and membrane structures required for cochlear hair-cell and photoreceptor function. Biallelic pathogenic variants cause Usher syndrome type 2A or nonsyndromic retinitis pigmentosa and can also produce isolated hearing loss.

  0 disease-causing and 1 uncertain variants in USH2A are linked to Retinal disorder.

• C3: Complement C3

  It is cleaved during complement activation to generate C3a and C3b, which amplify inflammation, opsonize targets, and drive formation of downstream complement complexes. Deficiency causes severe susceptibility to bacterial infection, while dysregulated activation contributes to complement-mediated kidney and inflammatory diseases.

  0 disease-causing and 0 uncertain variants in C3 are linked to Retinal disorder.

• CETP: Cholesteryl ester transfer protein

  It transfers cholesteryl esters and triglycerides between HDL and apoB-containing lipoproteins, strongly influencing circulating lipoprotein composition. Loss-of-function variants can raise HDL cholesterol, while pharmacologic CETP inhibition has been developed to lower atherosclerotic cardiovascular risk.

  0 disease-causing and 0 uncertain variants in CETP are linked to Retinal disorder.

• CFH: Complement factor H

  It restrains the alternative complement pathway on host surfaces and in plasma, protecting tissues from uncontrolled complement amplification. Pathogenic variants or risk alleles are associated with atypical hemolytic uremic syndrome, C3 glomerulopathy, and age-related macular degeneration.

  0 disease-causing and 0 uncertain variants in CFH are linked to Retinal disorder.

Weakly linked (only a few uncertain records): AIRE, BBS1, BBS2, CNGA1, EYS, MERTK, NR2E3 and RLBP1.

Known disease-causing variants in Retinal disorder

Which prediction tools work for Retinal disorder

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• MetaLR: 97 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CADD: 94 out of 100
• REVEL: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 91 out of 100
• phyloP: 89 out of 100

Same protein, different disease

• Severe early-childhood-onset retinal dystrophy is also caused by ABCA4 variants; they fall mostly in different places as the Retinal disorder variants (148 disease-causing).
• ABCA4-related retinopathy is also caused by ABCA4 variants; they fall mostly in different places as the Retinal disorder variants (60 disease-causing).
• Retinitis pigmentosa is also caused by ABCA4 variants; they fall mostly in different places as the Retinal disorder variants (58 disease-causing).
• Stargardt disease is also caused by ABCA4 variants; they fall mostly in different places as the Retinal disorder variants (41 disease-causing).
• Age related macular degeneration 9 is also caused by ABCA4 variants; they fall mostly in different places as the Retinal disorder variants (41 disease-causing).
• Vitelliform macular dystrophy 2 is also caused by BEST1 variants; they fall mostly in different places as the Retinal disorder variants (39 disease-causing).
• Autosomal recessive bestrophinopathy is also caused by BEST1 variants; they fall mostly in different places as the Retinal disorder variants (22 disease-causing).
• Autosomal dominant vitreoretinochoroidopathy is also caused by BEST1 variants; they fall mostly in different places as the Retinal disorder variants (9 disease-causing).
• BEST1-related dominant retinopathy is also caused by BEST1 variants; they fall mostly in different places as the Retinal disorder variants (3 disease-causing).
• Retinitis pigmentosa is also caused by RHO variants; they fall mostly in different places as the Retinal disorder variants (65 disease-causing).
• Pigmentary retinal dystrophy is also caused by RHO variants; they fall mostly in different places as the Retinal disorder variants (5 disease-causing).
• Congenital stationary night blindness autosomal dominant 3 is also caused by RHO variants; they fall mostly in different places as the Retinal disorder variants (3 disease-causing).

Diseases related to Retinal disorder

• Retinitis pigmentosa, also linked to ABCA4, BEST1, PRPH2, RHO and 1 more
• Age related macular degeneration 9, also linked to ABCA4, C3, CETP and CFH
• Cone-rod dystrophy, also linked to ABCA4, PRPH2 and USH2A
• Stargardt disease, also linked to ABCA4 and PRPH2
• Vitelliform macular dystrophy 2, also linked to BEST1 and PRPH2
• Atypical hemolytic-uremic syndrome, also linked to C3 and CFH
• Congenital stationary night blindness autosomal dominant 3, also linked to ABCA4 and RHO
• Pigmentary retinal dystrophy, also linked to PRPH2 and RHO
• Autosomal recessive retinitis pigmentosa, also linked to ABCA4 and USH2A
• Isolated macular dystrophy, also linked to ABCA4 and BEST1
• Leber congenital amaurosis, also linked to ABCA4
• Severe early-childhood-onset retinal dystrophy, also linked to ABCA4

Frequently asked questions

Which genes are linked to Retinal disorder?

In CATVariant, Retinal disorder is linked to 8 analyzed proteins: ABCA4 (Retinal-specific phospholipid-transporting ATPase ABCA4), BEST1 (Bestrophin-1), RHO (Rhodopsin), PRPH2 (Peripherin-2), USH2A (Usherin), C3 (Complement C3) and 2 more.

How many genetic variants are linked to Retinal disorder?

118 variants: 14 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 11 are of uncertain significance or have conflicting reports.

Which uncertain variants in Retinal disorder look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for Retinal disorder?

Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 0.94, based on 12 disease-causing and 172 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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