TMEFF1

protein-coding

transmembrane protein with EGF like and two follistatin like domains 1

Gene summary

Enables receptor ligand inhibitor activity. Involved in host-mediated suppression of symbiont invasion. Is active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C9orf2

MANE transcript

NM_003692.5

Inheritance

ClinVar variants

U:17

Top phenotype

hereditary predisposition to infections

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr9:100,473,149-100,577,636

External References & Databases

Ensembl (ENSG00000241697)

Transcript & Mutation Effects

hg38 • Region Span ~104.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hereditary predisposition to infectionsSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0015979

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMEFF1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 14

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003692.5. 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						0
missense			16 clinvar			16
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	17	0	0	17

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003692.5	RefSeq	NP_003683.2	10	MANE Select
ENST00000374879.5	Ensembl	ENSP00000364013.4	10	MANE Select
ENST00000906121.1	Ensembl	ENSP00000576180.1	9	Standard
ENST00000906121.2	Ensembl	ENSP00000576180.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

multicellular organism development

Cellular Component

plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000374879
Coding exons: 10
Length: 135359
Individuals with no LoFs: 125687
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 125705
p: 0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.10	148	191	0.776	0.00000881	2464
Missense (PolyPhen)		50	75.771	0.65988		958
Synonymous	0.533	61	66.5	0.917	0.00000315	694
Loss of Function	3.26	4	19.6	0.204	9.52e-7	267

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000063	0.000058	rare
Ashkenazi Jewish	0.00060	0.00060	rare
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May inhibit NODAL and BMP signaling during neural patterning (By similarity). May be a tumor suppressor in brain cancers. {ECO:0000250, ECO:0000269|PubMed:12743596}.;

Recessive Scores

pRec: 0.347

Intolerance Scores

RVIS EVS: -0.45
RVIS percentile EVS: 24

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.241

Gene Damage Prediction

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