ABLIM3

Chr 5

actin binding LIM protein family member 3

Also known as: HMFN1661

NCBI Gene: 22885 ENSG00000173210 UniProt: O94929 OMIM: 611305

The encoded protein functions as a scaffold protein that binds actin filaments and may stimulate ABRA-dependent transcriptional activity at adherens junctions. Mutations cause autosomal recessive retinal dystrophy with early childhood onset. This gene is highly constrained against loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the actin-binding LIM (abLIM) family of proteins. These proteins are characterized by an N-terminal LIM domain and a C-terminal dematin-like domain. The encoded protein interacts with actin filaments and may be a component of adherens junctions in several cell types. A variant of this gene may be associated with pain sensitivity in male human patients. [provided by RefSeq, Sep 2016]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.59

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.59LOEUF

pLI 0.000

Z-score 3.91

OE 0.41 (0.29–0.59)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.70Z-score

OE missense 0.90 (0.83–0.98)

381 obs / 421.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.41 (0.29–0.59)

0≤0.351.4

Missense OE?0.90 (0.83–0.98)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 21 / 51.2Missense obs/exp: 381 / 421.2Syn Z: 1.09

Background carrier burden — how many people carry a rare variant somewhere in ABLIM3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 45

874 rare PASS variants

Rare truncating (LoF)

1 in 1,800

105 rare PASS variants

Rare synonymous (reference)

1 in 120

315 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ABLIM3. 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 61	1 in 1,700
South Asian	~43k	1 in 47	1 in 1,300
Remaining (unassigned)	~30k	1 in 39	1 in 1,800
European (Finnish)	~27k	1 in 140	1 in 750
Admixed American	~22k	1 in 53	1 in 1,400
African / African American	~21k	1 in 51	1 in 1,500
East Asian	~20k	1 in 72	1 in 980
Ashkenazi Jewish	~13k	1 in 140	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 57	≈ 1 in 2,900

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