FANK1

Chr 10

fibronectin type III and ankyrin repeat domains 1

Also known as: HSD13

NCBI Gene: 92565 ENSG00000203780 UniProt: Q8TC84 OMIM: 611640

FANK1 encodes a protein that regulates apoptosis through activation of JUN and AP-1-mediated transcription. Mutations cause autosomal recessive intellectual disability with seizures and corpus callosum abnormalities. The gene is not highly constrained against loss-of-function variants, consistent with recessive inheritance patterns.

OMIM ResearchSummary from RefSeq, UniProt

Involved in regulation of DNA-templated transcription and regulation of apoptotic process. Located in chromatin; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.18

Clinical Summary— FANK1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

53 VUS of 71 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.18LOEUF

pLI 0.000

Z-score 0.94

OE 0.78 (0.53–1.18)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.55Z-score

OE missense 0.89 (0.78–1.01)

173 obs / 194.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.78 (0.53–1.18)

0≤0.351.4

Missense OE?0.89 (0.78–1.01)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 16 / 20.6Missense obs/exp: 173 / 194.8Syn Z: 0.75

This gene — mechanism propensity

0.6453th %ile

GOF

0.6053th %ile

LOF

0.3843th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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

71 submitted variants in ClinVar

ClinVar

Classification Summary

VUS53

Likely Benign1

Benign3

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	53	0	53
Likely Benign	1	0	1
Benign	1	2	3
Total	55	2	57

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

69 pathogenic / likely-pathogenic (of 76) ClinVar copy-number / structural variants overlap FANK1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →