KRTAP10-1

Chr 21

keratin associated protein 10-1

Also known as: KAP10.1, KAP18-1, KAP18.1, KRTAP10.1, KRTAP18-1, KRTAP18.1

NCBI Gene: 386677 ENSG00000215455 UniProt: P60331

The encoded protein forms a matrix with keratin intermediate filaments through extensive disulfide cross-linking, providing structural integrity to hair shafts. Mutations in this gene cause autosomal recessive woolly hair, a disorder characterized by tightly curled, fine hair texture that differs from normal hair. This gene is not highly constrained against loss-of-function variants, consistent with its tissue-specific role in hair structure.

Summary from RefSeq, UniProt

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Active trials

Pubs (1 yr)

P/LP submissions

P/LP missense

1.66

LOEUF

Multiple*

Mechanism· predicted

Clinical Summary— KRTAP10-1

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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

88 unique Pathogenic / Likely Pathogenic· 84 VUS of 186 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint

1.66LOEUF

pLI 0.000

Z-score 0.29

OE 0.88 (0.48–1.66)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint

-1.39Z-score

OE missense 1.31 (1.17–1.47)

212 obs / 162.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios

LoF OE0.88 (0.48–1.66)

0≤0.351.4

Missense OE1.31 (1.17–1.47)

0≤0.61.4

Synonymous OE1.67

0≤1.21.6

LoF obs/exp: 6 / 6.8Missense obs/exp: 212 / 162.1Syn Z: -4.43

0.90top 5%

GOF

0.84top 5%

LOF

0.3357th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction 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.