SHLD1
protein-codingshieldin complex subunit 1, the group of Shieldin complex
Gene summary
Involved in negative regulation of double-strand break repair via homologous recombination; positive regulation of double-strand break repair via nonhomologous end joining; and positive regulation of isotype switching. Located in site of double-strand break. [provided by Alliance of Genome Resources, Jul 2025]
- C20orf196
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~114.0 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 SHLD1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152504.4. 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 | 2 | 2 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 3 | 0 | 0 | 3 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_689717.2 | 2 | MANE Select | |
| Ensembl | ENSP00000305875.6 | 2 | MANE Select | |
| RefSeq | NP_001290406.1 | 2 | Standard | |
| RefSeq | NP_001290407.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- DNA repair
- positive regulation of isotype switching
- negative regulation of double-strand break repair via homologous recombination
- positive regulation of double-strand break repair via nonhomologous end joining
Molecular Function
- protein binding
Cellular Component
- chromosome
- site of double-strand break
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000303142
- Coding exons
- 2
- Length
- 113520
- Individuals with no LoFs
- 125726
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 16
- Defined
- 125742
- p
- 0.0000636
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.479 | 97 | 111 | 0.872 | 0.00000571 | 1351 |
| Missense (PolyPhen) | 27 | 27.744 | 0.97319 | 371 | ||
| Synonymous | -0.199 | 47 | 45.3 | 1.04 | 0.00000253 | 388 |
| Loss of Function | 1.57 | 2 | 6.24 | 0.320 | 2.63e-7 | 77 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the shieldin complex, which plays an important role in repair of DNA double-stranded breaks (DSBs). During G1 and S phase of the cell cycle, the complex functions downstream of TP53BP1 to promote non-homologous end joining (NHEJ) and suppress DNA end resection. Mediates various NHEJ-dependent processes including immunoglobulin class-switch recombination, and fusion of unprotected telomeres. {ECO:0000269|PubMed:29656893}.;
Intolerance Scores
- RVIS EVS
- 0.79
- RVIS percentile EVS
- 87.4
Essentials
- Essential (gene trap)
- N