THEMIS2

protein-coding

thymocyte selection associated family member 2

Gene summary

Predicted to be involved in T cell receptor signaling pathway and regulation of B cell activation. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C1orf38

MANE transcript

NM_001105556.3

Inheritance

—

ClinVar variants

U:100B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr1:27,872,543-27,886,685

External References & Databases

Ensembl (ENSG00000130775)

Transcript & Mutation Effects

hg38 • Region Span ~14.1 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 THEMIS2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 101

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001105556.3. 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			4 clinvar	3 clinvar		7
missense			96 clinvar	6 clinvar	1 clinvar	103
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	100	9	1	110

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001105556.3	RefSeq	NP_001099026.1	6	MANE Select
ENST00000373921.8	Ensembl	ENSP00000363031.3	6	MANE Select
NM_001039477.3	RefSeq	NP_001034566.1	3	Standard
NM_001286113.2	RefSeq	NP_001273042.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

inflammatory response
cell adhesion
T cell receptor signaling pathway

Molecular Function

protein binding

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373921
Coding exons: 6
Length: 14142
Individuals with no LoFs: 125711
Homozygous LoFs: 0
Heterozygous LoFs: 37
Defined: 125748
p: 0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.24	309	377	0.821	0.0000224	4134
Missense (PolyPhen)		104	143.18	0.72638		1646
Synonymous	1.07	140	157	0.891	0.00000871	1362
Loss of Function	2.52	8	20.3	0.395	9.29e-7	249

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00012	0.000099	rare
East Asian	0.000056	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00021	0.00021	rare
South Asian	0.00013	0.00013	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May constitute a control point in macrophage inflammatory response, promoting LPS-induced TNF production. {ECO:0000269|PubMed:20644716}.;

Recessive Scores

pRec: 0.0906

Intolerance Scores

RVIS EVS: -0.53
RVIS percentile EVS: 20.78

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N

Gene Damage Prediction

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