Intellectual disability-severe speech delay-mild dysmorphism syndrome: genes and variants
Intellectual disability-severe speech delay-mild dysmorphism syndrome is linked to 1 analyzed protein (FOXP1). 17 DNA variants are known to cause it; 41 more are uncertain, and 1 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Intellectual disability-severe speech delay-mild dysmorphism syndrome
FOXP1: Forkhead box protein P1
It regulates transcriptional programs in brain, heart, lung, and immune development and is especially important for neuronal differentiation and language-related circuits. Haploinsufficiency causes a neurodevelopmental syndrome with intellectual disability, speech and language impairment, and frequent autism-related features.
17 disease-causing and 41 uncertain variants in FOXP1 are linked to Intellectual disability-severe speech delay-mild dysmorphism syndrome.
Where Intellectual disability-severe speech delay-mild dysmorphism syndrome variants cluster
- FOXP1 Fork-head (positions 465–555): 15 of 17 disease-causing changes, 6.6× more than its size predicts.
Known disease-causing variants in Intellectual disability-severe speech delay-mild dysmorphism syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| FOXP1 R465G | 465 | Fork-head | Disease-causing (★★) |
| FOXP1 R514C | 514 | Fork-head | Disease-causing (★★) |
| FOXP1 R525Q | 525 | Fork-head | Disease-causing (★★) |
| FOXP1 T469I | 469 | Fork-head | Disease-causing (★★) |
| FOXP1 Y470F | 470 | Fork-head | Disease-causing (★★) |
| FOXP1 F502L | 502 | Fork-head | Disease-causing (★★) |
| FOXP1 R514P | 514 | Fork-head | Disease-causing (★) |
| FOXP1 R465T | 465 | Fork-head | Disease-causing (★) |
| FOXP1 L517R | 517 | Fork-head | Disease-causing (★) |
| FOXP1 F523L | 523 | Fork-head | Disease-causing (★) |
| FOXP1 Q476P | 476 | Fork-head | Disease-causing (★) |
| FOXP1 D451H | 451 | Disease-causing (★) | |
| FOXP1 I478S | 478 | Fork-head | Disease-causing (★) |
| FOXP1 A532V | 532 | Fork-head | Disease-causing (★) |
| FOXP1 S290T | 290 | Disease-causing (★) | |
| FOXP1 R514H | 514 | Fork-head | Disease-causing |
| FOXP1 S518N | 518 | Fork-head | Disease-causing |
Uncertain variants in Intellectual disability-severe speech delay-mild dysmorphism syndrome that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| FOXP1 F523S | 523 | Fork-head | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; F523L at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
Which prediction tools work for Intellectual disability-severe speech delay-mild dysmorphism syndrome
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- PolyPhen-2: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 93 out of 100
- CATVariant: 87 out of 100 (learned from overlapping clinical labels, so this is optimistic)
Frequently asked questions
Which genes are linked to Intellectual disability-severe speech delay-mild dysmorphism syndrome?
In CATVariant, Intellectual disability-severe speech delay-mild dysmorphism syndrome is linked to 1 analyzed protein: FOXP1 (Forkhead box protein P1).
How many genetic variants are linked to Intellectual disability-severe speech delay-mild dysmorphism syndrome?
81 variants: 17 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 41 are of uncertain significance or have conflicting reports.
Which uncertain variants in Intellectual disability-severe speech delay-mild dysmorphism syndrome look disease-causing?
1 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example FOXP1 F523S. These are leads for expert review, not diagnoses.
Which variant effect predictor works best for Intellectual disability-severe speech delay-mild dysmorphism syndrome?
Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.93, based on 11 disease-causing and 52 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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