NFAM1

protein-coding

NFAT activating protein with ITAM motif 1

Gene summary

The protein encoded by this gene is a type I membrane receptor that activates cytokine gene promoters such as the IL-13 and TNF-alpha promoters. The encoded protein contains an immunoreceptor tyrosine-based activation motif (ITAM) and is thought to regulate the signaling and development of B-cells. [provided by RefSeq, Jul 2008]

MANE transcript

NM_145912.8

Inheritance

—

ClinVar variants

U:40B:14

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr22:42,380,407-42,432,403

External References & Databases

Ensembl (ENSG00000235568)

Transcript & Mutation Effects

hg38 • Region Span ~52.0 kb

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GenCC 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 NFAM1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 48

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_145912.8. 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 clinvar	2 clinvar	3
missense			39 clinvar	8 clinvar	3 clinvar	50
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	40	9	5	54

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_145912.8	RefSeq	NP_666017.1	6	MANE Select
ENST00000329021.10	Ensembl	ENSP00000333680.5	6	MANE Select
NM_001318323.3	RefSeq	NP_001305252.1	4	Standard
NM_001371362.1	RefSeq	NP_001358291.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neutrophil degranulation
TCR
Innate Immune System
Immune System

Biological Process

positive regulation of cytokine production
inflammatory response
signal transduction
cell surface receptor signaling pathway
B cell differentiation

Molecular Function

transmembrane signaling receptor activity

Cellular Component

plasma membrane
integral component of membrane
azurophil granule membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000329021
Coding exons: 6
Length: 51986
Individuals with no LoFs: 125395
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125402
p: 0.0000279

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.266	140	149	0.939	0.00000859	1696
Missense (PolyPhen)		33	41.647	0.79236		539
Synonymous	-0.209	67	64.9	1.03	0.00000392	566
Loss of Function	1.02	8	11.8	0.678	6.13e-7	129

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.0000097	0.0000088	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May function in immune system as a receptor which activates via the calcineurin/NFAT-signaling pathway the downstream cytokine gene promoters. Activates the transcription of IL-13 and TNF-alpha promoters. May be involved in the regulation of B-cell, but not T-cell, development. Overexpression activates downstream effectors without ligand binding or antibody cross- linking. {ECO:0000269|PubMed:12615919, ECO:0000269|PubMed:15143214}.;

Recessive Scores

pRec: 0.0811

Intolerance Scores

LoFtool: 0.436
RVIS EVS: -0.14
RVIS percentile EVS: 43.77

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0901

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium