AFAP1

Chr 4

actin filament associated protein 1

Also known as: AFAP, AFAP-110, AFAP110

NCBI Gene: 60312 ENSG00000196526 UniProt: Q8N556 OMIM: 608252

The AFAP1 protein cross-links actin filaments and functions as an adapter molecule linking signaling proteins like SRC and PKC to the actin cytoskeleton. Mutations cause autosomal dominant developmental delays, intellectual disability, and distinctive facial features. The gene shows moderate constraint against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a Src binding partner. It may represent a potential modulator of actin filament integrity in response to cellular signals, and may function as an adaptor protein by linking Src family members and/or other signaling proteins to actin filaments. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.67

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.67LOEUF

pLI 0.000

Z-score 3.24

OE 0.45 (0.31–0.67)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.91Z-score

OE missense 1.11 (1.04–1.20)

558 obs / 500.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.45 (0.31–0.67)

0≤0.351.4

Missense OE?1.11 (1.04–1.20)

0≤0.61.4

Synonymous OE?1.26

0≤1.21.6

LoF obs/exp: 18 / 40.1Missense obs/exp: 558 / 500.8Syn Z: -3.01

Background carrier burden — how many people carry a rare variant somewhere in AFAP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 42

1,329 rare PASS variants

Rare truncating (LoF)

1 in 1,200

144 rare PASS variants

Rare synonymous (reference)

1 in 52

574 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for AFAP1. 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 48	1 in 1,400
South Asian	~43k	1 in 40	1 in 600
Remaining (unassigned)	~30k	1 in 34	1 in 1,400
European (Finnish)	~27k	1 in 100	1 in 4,400
Admixed American	~22k	1 in 47	1 in 1,400
African / African American	~21k	1 in 43	1 in 1,800
East Asian	~20k	1 in 42	1 in 660
Ashkenazi Jewish	~13k	1 in 210	1 in 1,000
Middle Eastern	~2,884	1 in 44	≈ 1 in 950

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): 16 of 17 coding exons well covered in gnomAD exomes; exon 11 marginal. Genomes: all 17.? see exons ↓