KRTAP5-8

Chr 11

keratin associated protein 5-8

Also known as: KRTAP5-2, KRTAP5.8, UHSKerB

NCBI Gene: 57830 ENSG00000241233 UniProt: O75690

The protein is a keratin-associated protein that forms the interfilamentous matrix in hair cortex through extensive disulfide cross-linking with hair keratins, creating the rigid hair shaft structure. Mutations cause woolly hair, autosomal recessive, which primarily affects hair texture and structure. This gene shows low constraint to loss-of-function variation, consistent with its tissue-specific expression pattern.

ResearchSummary from RefSeq, UniProt

Predicted to be a structural constituent of skin epidermis. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.89

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.89LOEUF

pLI 0.095

Z-score 0.07

OE 0.93 (0.26–1.89)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.32Z-score

OE missense 1.09 (0.93–1.29)

101 obs / 92.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.93 (0.26–1.89)

0≤0.351.4

Missense OE?1.09 (0.93–1.29)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 1 / 1.1Missense obs/exp: 101 / 92.3Syn Z: 0.25

Background carrier burden — how many people carry a rare variant somewhere in KRTAP5-8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

201 rare PASS variants

Rare truncating (LoF)

1 in 4,600

14 rare PASS variants

Rare synonymous (reference)

1 in 1,300

66 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KRTAP5-8. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 390	1 in 20,000
South Asian	~43k	1 in 150	1 in 950
Remaining (unassigned)	~30k	1 in 190	≈ 1 in 15,000
European (Finnish)	~27k	1 in 490	1 in 4,800
Admixed American	~22k	1 in 150	1 in 2,100
African / African American	~21k	1 in 320	1 in 1,500
East Asian	~20k	1 in 220	1 in 1,000
Ashkenazi Jewish	~13k	1 in 930	none seen
Middle Eastern	~2,884	1 in 150	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓