RHNO1

Chr 12

RAD9-HUS1-RAD1 interacting nuclear orphan 1

Also known as: C12orf32, HKMT1188, RHINO

The RHNO1 protein facilitates DNA repair through microhomology-mediated end-joining during mitosis and participates in DNA damage response signaling during S-phase by recruiting repair machinery to double-strand breaks. Mutations cause autosomal recessive intellectual disability with developmental delay, seizures, and distinctive facial features, typically presenting in early childhood. The gene shows low constraint to loss-of-function variation (pLI 0.003, LOEUF 1.25), which is consistent with recessive inheritance where heterozygous carriers are typically unaffected.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
4
Pubs (1 yr)
63
P/LP submissions
P/LP missense
1.25
LOEUF
DN
Mechanism· predicted
Clinical SummaryRHNO1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
63 unique Pathogenic / Likely Pathogenic· 6 VUS of 81 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.25LOEUF
pLI 0.003
Z-score 1.08
OE 0.60 (0.311.25)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.02Z-score
OE missense 1.00 (0.861.15)
127 obs / 127.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.60 (0.311.25)
00.351.4
Missense OE1.00 (0.861.15)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 5 / 8.4Missense obs/exp: 127 / 127.6Syn Z: 0.33
DN
0.7034th %ile
GOF
0.5759th %ile
LOF
0.3259th %ile

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

81 submitted variants in ClinVar

Classification Summary

Pathogenic60
Likely Pathogenic3
VUS6
Likely Benign3
60
Pathogenic
3
Likely Pathogenic
6
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
60
Likely Pathogenic
3
VUS
6
Likely Benign
3
Benign
0
Total72

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RHNO1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC