ARID5A

Chr 2

AT-rich interaction domain 5A

Also known as: MRF-1, MRF1, RP11-363D14

NCBI Gene: 10865 ENSG00000196843 UniProt: Q03989 OMIM: 611583

This gene encodes a DNA-binding protein that regulates transcription by binding to AT-rich promoter sequences and functions as an RNA-binding protein that stabilizes inflammation-related mRNAs including IL6 and STAT3. Mutations in ARID5A have not been definitively associated with human disease based on the available information. The gene shows high constraint against loss-of-function variants (pLI = 0.95, LOEUF = 0.35), suggesting that complete loss of function would likely be severe if disease-causing.

OMIM ResearchSummary from RefSeq, UniProt

Members of the ARID protein family, including ARID5A, have diverse functions but all appear to play important roles in development, tissue-specific gene expression, and regulation of cell growth (Patsialou et al., 2005 [PubMed 15640446]).[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

Clinical highlights

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

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.35

LOEUF

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.35LOEUF

pLI 0.945

Z-score 3.49

OE 0.11 (0.04–0.35)

Highly constrained

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

Missense Constraint?

1.67Z-score

OE missense 0.75 (0.67–0.83)

253 obs / 339.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.11 (0.04–0.35)

0≤0.351.4

Missense OE?0.75 (0.67–0.83)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 2 / 18.0Missense obs/exp: 253 / 339.5Syn Z: 1.17

Background carrier burden — how many people carry a rare variant somewhere in ARID5A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 76

762 rare PASS variants

Rare truncating (LoF)

1 in 1,100

75 rare PASS variants

Rare synonymous (reference)

1 in 110

344 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ARID5A. 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 96	1 in 1,000
South Asian	~43k	1 in 51	1 in 1,100
Remaining (unassigned)	~30k	1 in 58	1 in 1,600
European (Finnish)	~27k	1 in 190	1 in 1,600
Admixed American	~22k	1 in 80	1 in 2,700
African / African American	~21k	1 in 70	1 in 3,000
East Asian	~20k	1 in 74	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 190	1 in 2,500
Middle Eastern	~2,884	1 in 65	≈ 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): 6 of 7 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 7.? see exons ↓