DIAPH1

Chr 5

diaphanous related formin 1

Also known as: DFNA1, DIA1, DRF1, LFHL1, SCBMS, hDIA1, mDia1

NCBI Gene: 1729ENSG00000131504UniProt: O60610

This gene is a homolog of the Drosophila diaphanous gene, and has been linked to autosomal dominant, fully penetrant, nonsyndromic sensorineural progressive low-frequency hearing loss. Actin polymerization involves proteins known to interact with diaphanous protein in Drosophila and mouse. It has therefore been speculated that this gene may have a role in the regulation of actin polymerization in hair cells of the inner ear. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDeafness, autosomal dominant 1, with or without thrombocytopenia
UniProtSeizures, cortical blindness, and microcephaly syndrome

Clinical highlights

Gene-disease validity (ClinGen)
DIAPH1-related sensorineural hearing loss-thrombocytopenia syndrome · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
0
Active trials
39
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.32
LOEUF· LoF intol.
Multiple*
Mechanism· predicted
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GeneReview available — DIAPH1
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.32LOEUF
pLI 0.915
Z-score 5.80
OE 0.20 (0.13–0.32)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
1.65Z-score
OE missense 0.82 (0.76–0.88)
535 obs / 653.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.20 (0.13–0.32)
0≤0.351.4
Missense OE?0.82 (0.76–0.88)
0≤0.61.4
Synonymous OE?1.05
0≤1.21.6
LoF obs/exp: 12 / 60.8Missense obs/exp: 535 / 653.8Syn Z: -0.65

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

DIAPH1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients