RNF44

Chr 5

ring finger protein 44

NCBI Gene: 22838 ENSG00000146083 UniProt: Q7L0R7 OMIM: 619283

The encoded protein contains a RING finger domain that mediates protein-protein and protein-DNA interactions. Mutations cause autosomal recessive intellectual disability with seizures and microcephaly. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.502), suggesting some intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq

The protein encoded by this gene contains a RING finger, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.50

Clinical Summary— RNF44

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

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ClinVar Variants

88 VUS of 111 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.50LOEUF

pLI 0.270

Z-score 3.23

OE 0.24 (0.12–0.50)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.39Z-score

OE missense 0.93 (0.83–1.04)

209 obs / 225.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.12–0.50)

0≤0.351.4

Missense OE?0.93 (0.83–1.04)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 5 / 20.9Missense obs/exp: 209 / 225.7Syn Z: -1.44

This gene — mechanism propensity

0.6551th %ile

GOF

0.4085th %ile

LOF

0.55top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

111 submitted variants in ClinVar

ClinVar

Classification Summary

VUS88

Likely Benign3

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	88	0	88
Likely Benign	3	0	3
Benign	0	1	1
Total	91	1	92

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

View in ClinVar →

52 pathogenic / likely-pathogenic (of 58) ClinVar copy-number / structural variants overlap RNF44 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →