TM4SF19

protein-coding

transmembrane 4 L six family member 19

Gene summary

The protein encoded by this gene is a member of the four-transmembrane L6 superfamily. Members of this family function in various cellular processes including cell proliferation, motility, and adhesion via their interactions with integrins. In human brain tissue, this gene is expressed at high levels in the parietal lobe, occipital lobe, hippocampus, pons, white matter, corpus callosum, and cerebellum. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2017]

MANE transcript

NM_138461.4

Inheritance

—

ClinVar variants

U:28B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.89

Max pathogenic AF

—

Genomic locus

chr3:196,319,342-196,338,503

External References & Databases

Ensembl (ENSG00000145107)

Transcript & Mutation Effects

hg38 • Region Span ~19.2 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 TM4SF19 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 33

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138461.4. 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			2 clinvar			2
missense			25 clinvar	6 clinvar		31
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	28	6	0	34

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138461.4	RefSeq	NP_612470.2	4	MANE Select
ENST00000273695.4	Ensembl	ENSP00000273695.4	4	MANE Select
NM_001204897.2	RefSeq	NP_001191826.1	4	Standard
NM_001204898.2	RefSeq	NP_001191827.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000273695
Coding exons: 4
Length: 19162
Individuals with no LoFs: 125676
Homozygous LoFs: 0
Heterozygous LoFs: 70
Defined: 125746
p: 0.000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.698	94	115	0.817	0.00000597	1317
Missense (PolyPhen)		41	47.002	0.87231		584
Synonymous	-0.232	52	49.9	1.04	0.00000269	465
Loss of Function	0.323	9	10.1	0.890	5.96e-7	96

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0029	0.0029	notable
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000088	0.000088	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.633
RVIS EVS: 0.9
RVIS percentile EVS: 89.39

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0415

Gene Damage Prediction

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