FAM111B

Chr 11

FAM111 trypsin like peptidase B

Also known as: CANP, POIKTMP

NCBI Gene: 374393 ENSG00000189057 UniProt: Q6SJ93

The protein functions as a serine protease with a trypsin-like peptidase domain. Mutations cause hereditary fibrosing poikiloderma, an autosomal dominant disorder characterized by mottled skin pigmentation, telangiectasia, epidermal atrophy, tendon contractures, myopathy, and progressive pulmonary fibrosis. The condition primarily affects skin, muscle, connective tissue, and respiratory systems.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein with a trypsin-like cysteine/serine peptidase domain in the C-terminus. Mutations in this gene are associated with an autosomal dominant form of hereditary fibrosing poikiloderma (HFP). Affected individuals display mottled pigmentation, telangiectasia, epidermal atrophy, tendon contractures, and progressive pulmonary fibrosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms. A paralog of this gene which also has a trypsin‐like peptidase domain, FAM111A, is located only 16 kb from this gene on human chromosome 11q12.1. [provided by RefSeq, Apr 2014]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPoikiloderma, hereditary fibrosing, with tendon contractures, myopathy, and pulmonary fibrosis

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · hereditary sclerosing poikiloderma with tendon and pulmonary involvement · AD · ClinGen 2023

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.88

LOEUF

Multiple*

Mechanism· predicted

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GeneReview available — FAM111B

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.88LOEUF

pLI 0.099

Z-score 0.13

OE 0.87 (0.25–1.88)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.23Z-score

OE missense 1.03 (0.95–1.12)

402 obs / 389.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.87 (0.25–1.88)

0≤0.351.4

Missense OE?1.03 (0.95–1.12)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 1 / 1.1Missense obs/exp: 402 / 389.0Syn Z: 0.60

Background carrier burden — how many people carry a rare variant somewhere in FAM111B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 82

950 rare PASS variants

Rare truncating (LoF)

1 in 600

161 rare PASS variants

Rare synonymous (reference)

1 in 150

319 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FAM111B. 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 110	1 in 300
South Asian	~43k	1 in 72	1 in 250
Remaining (unassigned)	~30k	1 in 68	1 in 670
European (Finnish)	~27k	1 in 320	1 in 620
Admixed American	~22k	1 in 79	1 in 410
African / African American	~21k	1 in 61	1 in 330
East Asian	~20k	1 in 68	1 in 310
Ashkenazi Jewish	~13k	1 in 340	1 in 1,500
Middle Eastern	~2,884	1 in 64	≈ 1 in 580

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 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓