SPECC1
Chr 17sperm antigen with calponin homology and coiled-coil domains 1
Also known as: CYTSB, HCMOGT-1, HCMOGT1, NSP, NSP5
The SPECC1 protein is a nuclear-localized member of the cytospin-A family that is highly constrained against loss-of-function variants. Mutations cause Opitz G/BBB syndrome, an autosomal dominant disorder characterized by midline developmental defects including hypertelorism, cleft lip/palate, and genitourinary abnormalities. The gene's high constraint (pLI ~0.0009, LOEUF 0.49) reflects its critical role in normal midline development during embryogenesis.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
18 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | — | — | — | — | 16 |
Likely Pathogenic | — | — | — | — | 0 |
VUS | — | — | — | — | 2 |
Likely Benign | — | — | — | — | 0 |
Benign | — | — | — | — | 0 |
| Total | — | 18 | |||
Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SPECC1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools