TMEM199

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				7 clinvar		7
missense		2 clinvar	42 clinvar	1 clinvar	4 clinvar	49
nonsense						0
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	1	3	42	8	4	58

Highest pathogenic variant AF is 0.0000131403

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 0 of 0 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
No transcripts match your selected source or search query.

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cellular iron ion homeostasis
lysosomal lumen acidification
cellular response to increased oxygen levels
vacuolar proton-transporting V-type ATPase complex assembly
lysosomal protein catabolic process

Molecular Function

protein binding

Cellular Component

lysosome
endoplasmic reticulum
endoplasmic reticulum membrane
integral component of membrane
vacuolar proton-transporting V-type ATPase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000292114
Coding exons: 6
Length: 24113
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 19
Defined: 125748
p: 0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.246	132	124	1.06	0.00000724	1302
Missense (PolyPhen)		49	49.545	0.98899		510
Synonymous	-0.873	61	52.9	1.15	0.00000300	455
Loss of Function	0.539	8	9.82	0.814	4.19e-7	119

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.000098	0.000097	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Accessory component of the proton-transporting vacuolar (V)-ATPase protein pump involved in intracellular iron homeostasis. In aerobic conditions, required for intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation. Necessary for endolysosomal acidification and lysosomal degradation (PubMed:28296633). May be involved in Golgi homeostasis (PubMed:26833330). {ECO:0000269|PubMed:26833330, ECO:0000269|PubMed:28296633}.;
Disease: DISEASE: Congenital disorder of glycosylation 2P (CDG2P) [MIM:616829]: A form of congenital disorder of glycosylation, a genetically heterogeneous group of autosomal recessive, multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG2P is characterized by mild metabolic dysfunction, primarily affecting the liver. Psychomotor development is normal. {ECO:0000269|PubMed:26833330}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.108

Intolerance Scores

RVIS EVS: 0.37
RVIS percentile EVS: 75.29

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.575

Gene Damage Prediction

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