NIF3L1

Chr 2

NGG1 interacting factor 3 like 1

Also known as: ALS2CR1, CALS-7, MDS015

NIF3L1 encodes a protein that functions as a transcriptional corepressor, negatively regulating genes involved in neuronal differentiation through interaction with COPS2. Mutations cause autosomal recessive developmental and epileptic encephalopathy with severe intellectual disability and early-onset seizures. This gene is not highly constrained against loss-of-function mutations.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 1.28
Clinical SummaryNIF3L1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
32 unique Pathogenic / Likely Pathogenic· 61 VUS of 107 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.28LOEUF
pLI 0.000
Z-score 0.69
OE 0.82 (0.541.28)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.22Z-score
OE missense 1.04 (0.931.16)
226 obs / 216.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.82 (0.541.28)
00.351.4
Missense OE1.04 (0.931.16)
00.61.4
Synonymous OE0.87
01.21.6
LoF obs/exp: 14 / 17.1Missense obs/exp: 226 / 216.9Syn Z: 0.96

ClinVar Variant Classifications

107 submitted variants in ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic1
VUS61
Likely Benign6
31
Pathogenic
1
Likely Pathogenic
61
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
31
0
31
Likely Pathogenic
0
0
1
0
1
VUS
0
58
3
0
61
Likely Benign
0
5
0
1
6
Benign
0
0
0
0
0
Total06335199

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

View in ClinVar →

Protein Context — Lollipop Plot

NIF3L1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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