REPIN1

Chr 7

replication initiator 1

Also known as: AP4, RIP60, ZNF464, Zfp464

NCBI Gene: 29803ENSG00000214022UniProt: Q9BWE0

Enables sequence-specific DNA binding activity. Predicted to be involved in regulation of fatty acid transport and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within positive regulation of D-glucose import. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

181
ClinVar variants
66
Pathogenic / LP
0.09
pLI score
0
Active trials
Clinical Summary— REPIN1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.
📋
ClinVar Variants
66 Pathogenic / Likely Pathogenic· 109 VUS of 181 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.54LOEUF
pLI 0.095
Z-score 3.16
OE 0.27 (0.15–0.54)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.43Z-score
OE missense 0.67 (0.61–0.74)
295 obs / 438.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.27 (0.15–0.54)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.61–0.74)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.89
0≤1.21.6
LoF obs/exp: 6 / 22.0Missense obs/exp: 295 / 438.4Syn Z: 1.15

ClinVar Variant Classifications

181 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic63
Likely Pathogenic3
VUS109
Likely Benign6
63
Pathogenic
3
Likely Pathogenic
109
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
63
0
63
Likely Pathogenic
0
0
3
0
3
VUS
1
102
6
0
109
Likely Benign
0
5
0
1
6
Benign
0
0
0
0
0
Total1107721181

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

View in ClinVar →

Protein Context — Lollipop Plot

REPIN1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
REPIN1 regulates iron metabolism and osteoblast apoptosis in osteoporosis.
Xia Y et al.·Cell Death Dis
2023
Metabolic effects of genetic variation in the human REPIN1 gene.
Krüger J et al.·Int J Obes (Lond)
2019
A Human REPIN1 Gene Variant: Genetic Risk Factor for the Development of Nonalcoholic Fatty Liver Disease.
Abshagen K et al.·Clin Transl Gastroenterol
2020
Hsa-mir-127 impairs survival of patients with glioma and promotes proliferation, migration and invasion of cancerous cells by modulating replication initiator 1.
Wang Y et al.·Neuroreport
2018Cohort
Peptide ARHGEF9 Inhibits Glioma Progression via PI3K/AKT/mTOR Pathway.
Huang J et al.·Dis Markers
2023
Identifying Genetic Factors of Polycystic Ovary Syndrome in Women with Epilepsy: A Whole-Genome Sequencing Study.
Lai W et al.·Neuroendocrinology
2024
Genetic profiling of azoospermic men to identify the etiology and predict reproductive potential.
Cheung S et al.·J Assist Reprod Genet
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools