CORO1A

Chr 16AR

coronin 1A

Also known as: CLABP, CLIPINA, HCORO1, IMD8, TACO, p57

NCBI Gene: 11151 ENSG00000102879 UniProt: P31146 OMIM: 605000

This gene encodes coronin-1A, a cytoskeletal protein that regulates cell motility through plasma membrane invagination and protrusion formation, and prevents phagosome-lysosome fusion in mycobacteria-infected cells. Mutations cause autosomal recessive immunodeficiency 8, a severe combined immunodeficiency typically presenting in infancy. The gene is highly constrained against loss-of-function variation (pLI 0.97, LOEUF 0.32), indicating that functional copies are essential for normal development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Alternative splicing results in multiple transcript variants. A related pseudogene has been defined on chromosome 16. [provided by RefSeq, Sep 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Immunodeficiency 8MIM #615401

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · severe combined immunodeficiency due to CORO1A deficiency · AR · ClinGen 2022

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.32

LOEUF· LoF intol.

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Mechanism

📖

GeneReview available — CORO1A

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.32LOEUF

pLI 0.970

Z-score 3.69

OE 0.10 (0.04–0.32)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.48Z-score

OE missense 0.58 (0.51–0.66)

162 obs / 278.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.10 (0.04–0.32)

0≤0.351.4

Missense OE?0.58 (0.51–0.66)

0≤0.61.4

Synonymous OE?1.22

0≤1.21.6

LoF obs/exp: 2 / 19.7Missense obs/exp: 162 / 278.2Syn Z: -1.85

Background carrier burden — how many people carry a rare variant somewhere in CORO1A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

478 rare PASS variants

Rare truncating (LoF)

1 in 2,500

60 rare PASS variants

Rare synonymous (reference)

1 in 110

292 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CORO1A. 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 200	1 in 3,800
South Asian	~43k	1 in 110	1 in 1,400
Remaining (unassigned)	~30k	1 in 140	1 in 1,400
European (Finnish)	~27k	1 in 610	1 in 2,200
Admixed American	~22k	1 in 130	1 in 3,600
African / African American	~21k	1 in 130	≈ 1 in 4,900
East Asian	~20k	1 in 180	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 290	none seen
Middle Eastern	~2,884	1 in 160	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): 9 of 10 coding exons well covered in gnomAD exomes; exon 11 poorly covered. Genomes: 8 of 10 (exons 7, 11 below).? see exons ↓