CXXC5

Chr 5

CXXC finger protein 5

Also known as: CF5, HSPC195, RINF, WID

NCBI Gene: 51523ENSG00000171604UniProt: Q7LFL8

The protein encoded by this gene is a retinoid-inducible nuclear protein containing a CXXC-type zinc finger motif. The encoded protein is involved in myelopoiesis, is required for DNA damage-induced p53 activation, regulates the differentiation of C2C12 myoblasts into myocytes, and negatively regulates cutaneous wound healing. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Nov 2015]

66
ClinVar variants
12
Pathogenic / LP
0.89
pLI score
0
Active trials
Clinical Summary— CXXC5
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.89) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 48 VUS of 66 total submissions

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 0.889
Z-score 2.47
OE 0.00 (0.00–0.42)
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.
1.58Z-score
OE missense 0.70 (0.62–0.80)
157 obs / 223.4 exp
Tolerant

Mild missense constraint

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.0.00 (0.00–0.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.62–0.80)
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.0.92
0≤1.21.6
LoF obs/exp: 0 / 7.1Missense obs/exp: 157 / 223.4Syn Z: 0.61

ClinVar Variant Classifications

66 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
VUS48
Likely Benign6
12
Pathogenic
48
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
12
0
12
Likely Pathogenic
0
0
0
0
0
VUS
0
42
6
0
48
Likely Benign
0
4
1
1
6
Benign
0
0
0
0
0
Total04619166

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

View in ClinVar →

Protein Context — Lollipop Plot

CXXC5 · 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
Wnt Signalling in Acute Myeloid Leukaemia.
Gruszka AM et al.·Cells
2019Review
Context-dependent tumor-suppressive BMP signaling in diffuse intrinsic pontine glioma regulates stemness through epigenetic regulation of CXXC5.
Sun Y et al.·Nat Cancer
2022
Therapeutic targeting of Wnt antagonists by small molecules for treatment of osteoporosis.
Abhishek Shah A et al.·Biochem Pharmacol
2024Review
Inhibition of CXXC5 function reverses obesity-related metabolic diseases.
Seo SH et al.·Clin Transl Med
2022
CXXC5 expression in prostate cancer: implications for cancer progression.
Benedetti I et al.·Int J Exp Pathol
2017
Inhibition of CXXC5 function rescues Alzheimer's disease phenotypes by restoring Wnt/β-catenin signaling pathway.
Yoon M et al.·Pharmacol Res
2023
Targeting Wnt signaling pathway with small-molecule therapeutics for treating osteoporosis.
Ahamad S et al.·Bioorg Chem
2025Review
A CpG island promoter drives the CXXC5 gene expression.
Yaşar P et al.·Sci Rep
2021
Revolutionary Approaches to Hair Regrowth: Follicle Neogenesis, Wnt/ß-Catenin Signaling, and Emerging Therapies.
Mehta A et al.·Cells
2025Review
CXXC5 is a negative-feedback regulator of the Wnt/β-catenin pathway involved in osteoblast differentiation.
Kim HY et al.·Cell Death Differ
2015
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