KRTAP10-2

Chr 21

keratin associated protein 10-2

Also known as: KAP10.2, KAP18-2, KAP18.2, KRTAP10.2, KRTAP18-2, KRTAP18.2

NCBI Gene: 386679 ENSG00000205445 UniProt: P60368

The protein is a high-sulfur keratin-associated protein that forms a matrix with keratin intermediate filaments through extensive disulfide cross-linking, providing structural integrity to hair shafts. Mutations in this gene have not been definitively associated with any recognized disease phenotypes in current medical literature. The gene shows tolerance to loss-of-function variants, consistent with its specific role in hair fiber structure rather than essential cellular processes.

Summary from RefSeq, UniProt

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Active trials

Pubs (1 yr)

P/LP submissions

P/LP missense

1.81

LOEUF

Multiple*

Mechanism· predicted

Clinical Summary— KRTAP10-2

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.

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ClinVar Variants

88 unique Pathogenic / Likely Pathogenic· 54 VUS of 150 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

1.81LOEUF

pLI 0.351

Z-score 0.74

OE 0.00 (0.00–1.81)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint

-1.08Z-score

OE missense 1.26 (1.11–1.43)

172 obs / 136.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios

LoF OE0.00 (0.00–1.81)

0≤0.351.4

Missense OE1.26 (1.11–1.43)

0≤0.61.4

Synonymous OE1.46

0≤1.21.6

LoF obs/exp: 0 / 0.6Missense obs/exp: 172 / 136.4Syn Z: -2.76

0.89top 5%

GOF

0.80top 10%

LOF

0.3941th %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.