ARID5A

Chr 2

AT-rich interaction domain 5A

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

NCBI Gene: 10865 ENSG00000196843 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…

LOFmechanismLOEUF 0.35

Clinical Summary— ARID5A

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

93 VUS of 104 total submissions

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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

This gene — mechanism propensity

0.3991th %ile

GOF

0.3590th %ile

LOF

0.75top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.35

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

104 submitted variants in ClinVar

ClinVar

Classification Summary

VUS93

Likely Benign6

Conflicting1

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	2	91	0	0	93
Likely Benign	0	3	1	2	6
Benign	0	0	0	0	0
Conflicting	—				1
Total	2	94	1	2	100

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

32 pathogenic / likely-pathogenic (of 65) ClinVar copy-number / structural variants overlap ARID5A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →