NFIX

Chr 19

nuclear factor I X

Also known as: CTF, MALNS, MRSHSS, NF-I/X, NF1-X, NF1A, SOTOS2

NCBI Gene: 4784ENSG00000008441UniProt: Q14938

The protein encoded by this gene is a transcription factor that binds the palindromic sequence 5'-TTGGCNNNNNGCCAA-3 in viral and cellular promoters. The encoded protein can also stimulate adenovirus replication in vitro. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2012]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMalan syndrome
UniProtMarshall-Smith syndrome

Clinical highlights

Gene-disease validity (ClinGen)
Marshall-Smith syndrome · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
44
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.15
LOEUF· LoF intol.
LOF
Mechanism· G2P
📖
GeneReview available — NFIX
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.15LOEUF
pLI 0.999
Z-score 4.15
OE 0.00 (0.00–0.15)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
4.08Z-score
OE missense 0.29 (0.24–0.36)
78 obs / 264.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.00 (0.00–0.15)
0≤0.351.4
Missense OE?0.29 (0.24–0.36)
0≤0.61.4
Synonymous OE?0.89
0≤1.21.6
LoF obs/exp: 0 / 20.1Missense obs/exp: 78 / 264.8Syn Z: 0.96

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

NFIX · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients