ERCC6L2

Chr 9AR

ERCC excision repair 6 like 2

Also known as: BMFS2, C9orf102, HEBO, RAD26L, SR278

The ERCC6L2 protein is a Snf2 family helicase that promotes double-strand break repair by controlling DNA end-joining and restricting DNA end resection, while also facilitating replication of complex DNA regions and maintaining chromatin structure. Mutations cause bone marrow failure syndrome 2, inherited in an autosomal recessive pattern. This gene is not highly constrained against loss-of-function variants (pLI near zero), suggesting the pathogenic variants may involve other mechanisms.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.681 OMIM phenotype
Clinical SummaryERCC6L2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 338 VUS of 500 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — ERCC6L2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.68LOEUF
pLI 0.000
Z-score 3.13
OE 0.45 (0.310.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.64Z-score
OE missense 0.91 (0.830.99)
334 obs / 368.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.45 (0.310.68)
00.351.4
Missense OE0.91 (0.830.99)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 17 / 37.7Missense obs/exp: 334 / 368.4Syn Z: -0.85
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveERCC6L2-related bone marrow failure syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6938th %ile
GOF
0.4184th %ile
LOF
0.3745th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

500 submitted variants in ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic2
VUS338
Likely Benign142
9
Pathogenic
2
Likely Pathogenic
338
VUS
142
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
0
0
9
Likely Pathogenic
2
0
0
0
2
VUS
2
335
1
0
338
Likely Benign
0
3
17
122
142
Benign
0
0
0
0
0
Total1333818122491

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

View in ClinVar →

Protein Context — Lollipop Plot

ERCC6L2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC