HMCES
protein-coding5-hydroxymethylcytosine binding, ES cell specific
Gene summary
Enables DNA-(abasic site) binding activity; protein-DNA covalent cross-linking activity; and single-stranded DNA binding activity. Involved in interstrand cross-link repair; protein-DNA covalent cross-linking repair; and somatic hypermutation of immunoglobulin genes. Is active in replication fork. [provided by Alliance of Genome Resources, Jul 2025]
- C3orf37
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~27.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HMCES variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020187.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 58 | 2 | 60 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 58 | 2 | 1 | 61 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_064572.2 | 6 | MANE Select | |
| Ensembl | ENSP00000372955.3 | 6 | MANE Select | |
| RefSeq | NP_001006109.1 | 6 | Standard | |
| RefSeq | NP_001350810.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- proteolysis
- biological_process
Molecular Function
- molecular_function
- DNA binding
- peptidase activity
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000383463
- Coding exons
- 6
- Length
- 27359
- Individuals with no LoFs
- 125697
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 51
- Defined
- 125748
- p
- 0.000203
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0978 | 200 | 196 | 1.02 | 0.0000101 | 2307 |
| Missense (PolyPhen) | 65 | 68.959 | 0.94259 | 817 | ||
| Synonymous | 1.22 | 58 | 71.0 | 0.816 | 0.00000346 | 676 |
| Loss of Function | 1.20 | 13 | 18.6 | 0.700 | 9.58e-7 | 202 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00099 | 0.00098 | rare |
| Latino/Admixed American | 0.00014 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000097 | 0.000097 | rare |
| South Asian | 0.00040 | 0.00039 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Specifically binds 5-hydroxymethylcytosine (5hmC)- containing DNA in stem cells, suggesting that it acts as a specific reader of 5hmC in stem cells (By similarity). May act as a peptidase; experimental evidences are however required to confirm this prediction (PubMed:23945014). {ECO:0000250, ECO:0000269|PubMed:23945014}.;
Intolerance Scores
- RVIS EVS
- -0.54
- RVIS percentile EVS
- 20.54
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |