HJURP

Chr 2

Holliday junction recognition protein

Also known as: FAKTS, URLC9, hFLEG1

NCBI Gene: 55355ENSG00000123485UniProt: Q8NCD3

The protein acts as a specific chaperone for the centromeric histone variant CENPA, playing a central role in incorporating and maintaining CENPA at centromeres during chromosome segregation. Mutations cause autosomal recessive primary microcephaly with growth retardation and intellectual disability. This gene is extremely intolerant to loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
16
Pubs (1 yr)
39
P/LP submissions
0%
P/LP missense
0.79
LOEUF
DN
Mechanism· predicted
Clinical Summary— HJURP
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
39 unique Pathogenic / Likely Pathogenic· 113 VUS of 189 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.79LOEUF
pLI 0.000
Z-score 2.49
OE 0.52 (0.35–0.79)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.30Z-score
OE missense 1.04 (0.96–1.13)
442 obs / 424.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.52 (0.35–0.79)
0≤0.351.4
Missense OE1.04 (0.96–1.13)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 16 / 30.9Missense obs/exp: 442 / 424.8Syn Z: 0.24
DN
0.6259th %ile
GOF
0.5857th %ile
LOF
0.4135th %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

189 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic2
VUS113
Likely Benign21
37
Pathogenic
2
Likely Pathogenic
113
VUS
21
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
37
0
37
Likely Pathogenic
0
0
2
0
2
VUS
0
107
6
0
113
Likely Benign
0
20
0
1
21
Benign
0
0
0
0
0
Total0127451173

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

View in ClinVar →

Protein Context — Lollipop Plot

HJURP · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients