SHPRH

Chr 6

SNF2 histone linker PHD RING helicase

Also known as: RAD5, bA545I5.2

NCBI Gene: 257218ENSG00000146414UniProt: Q149N8

SHPRH is a ubiquitously expressed protein that contains motifs characteristics of several DNA repair proteins, transcription factors, and helicases. SHPRH is a functional homolog of S. cerevisiae RAD5 (Unk et al., 2006 [PubMed 17108083]).[supplied by OMIM, Mar 2008]

98
ClinVar variants
11
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SHPRH
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 82 VUS of 98 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

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.
0.42LOEUF
pLI 0.000
Z-score 6.21
OE 0.31 (0.23–0.42)
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.
2.33Z-score
OE missense 0.78 (0.73–0.83)
694 obs / 889.2 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.0.31 (0.23–0.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.73–0.83)
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.1.04
0≤1.21.6
LoF obs/exp: 29 / 93.9Missense obs/exp: 694 / 889.2Syn Z: -0.52

ClinVar Variant Classifications

98 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
VUS82
Likely Benign3
Benign2
11
Pathogenic
82
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
0
0
0
VUS
0
77
5
0
82
Likely Benign
0
1
1
1
3
Benign
0
1
1
0
2
Total07918198

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

View in ClinVar →

Protein Context — Lollipop Plot

SHPRH · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The Human RAD5 Homologs, HLTF and SHPRH, Have Separate Functions in DNA Damage Tolerance Dependent on The DNA Lesion Type.
Seelinger M et al.·Biomolecules
2020
Integrative genomics identifies SHPRH as a tumor suppressor gene in lung adenocarcinoma that regulates DNA damage response.
Nagelberg AL et al.·Br J Cancer
2024
Novel Insights Into Small Open Reading Frame-Encoded Micropeptides in Glioblastoma.
Wang M et al.·Cell Biol Int
2025Review
Axitinib blocks Wnt/β-catenin signaling and directs asymmetric cell division in cancer.
Qu Y et al.·Proc Natl Acad Sci U S A
2016
hMMS2 serves a redundant role in human PCNA polyubiquitination.
Brun J et al.·BMC Mol Biol
2008
Exome-wide analysis of bi-allelic alterations identifies a Lynch phenotype in The Cancer Genome Atlas.
Buckley AR et al.·Genome Med
2018
Relationship between autoimmunity and COPD: an investigation based on proteomic profiling and antinuclear antibody screening.
Das S et al.·J Immunoassay Immunochem
2025
A Combination of Microarray-Based Profiling and Biocomputational Analysis Identified miR331-3p and hsa-let-7d-5p as Potential Biomarkers of Ulcerative Colitis Progression to Colorectal Cancer.
Chacon-Millan P et al.·Int J Mol Sci
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