NIF3L1

Chr 2

NGG1 interacting factor 3 like 1

Also known as: ALS2CR1, CALS-7, MDS015

NCBI Gene: 60491 ENSG00000196290 UniProt: Q9GZT8 OMIM: 605778

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA polymerase II-specific DNA-binding transcription factor binding activity and identical protein binding activity. Involved in positive regulation of DNA-templated transcription. Located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 1.28

Clinical Summary— NIF3L1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

58 VUS of 72 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.28LOEUF

pLI 0.000

Z-score 0.69

OE 0.82 (0.54–1.28)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.22Z-score

OE missense 1.04 (0.93–1.16)

226 obs / 216.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.82 (0.54–1.28)

0≤0.351.4

Missense OE?1.04 (0.93–1.16)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 14 / 17.1Missense obs/exp: 226 / 216.9Syn Z: 0.96

ClinVar Variant Classifications

72 submitted variants in ClinVar

ClinVar

Classification Summary

VUS58

Likely Benign6

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	58	0	58
Likely Benign	5	1	6
Benign	0	0	0
Total	63	1	64

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

View in ClinVar →

32 pathogenic / likely-pathogenic (of 35) ClinVar copy-number / structural variants overlap NIF3L1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →