TMEM107

protein-coding

transmembrane protein 107

Gene summary

This gene encodes a transmembrane protein and component of the primary cilia transition zone. The encoded protein regulates ciliogenesis and ciliary protein composition. Human fibroblasts expressing a mutant allele of this gene exhibit reduced numbers of cilia, altered cilia length, and impaired sonic hedgehog signaling. In human patients, different mutations in this gene cause different ciliopathies, including Meckel-Gruber syndrome and orofaciodigital syndrome. [provided by RefSeq, May 2017]

MANE transcript

NM_183065.4

Inheritance

ClinVar variants

P:8U:45B:26

Top phenotype

Joubert syndrome 29; Meckel syndrome 13; Orofaciodigital syndrome XVI

gnomAD constraint

pLI —, LoF o/e 1.36

Max pathogenic AF

—

Genomic locus

chr17:8,172,457-8,176,399

External References & Databases

Ensembl (ENSG00000179029)

Transcript & Mutation Effects

hg38 • Region Span ~3.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

ciliopathySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0005308

Submitter: PanelApp Australia

Meckel syndrome 13STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033044

Submitter: Labcorp Genetics (formerly Invitae)

orofaciodigital syndrome 16LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0033045

Submitter: Labcorp Genetics (formerly Invitae)

Meckel syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018921

Submitter: Orphanet

ciliopathyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0005308

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Joubert syndrome 29; Meckel syndrome 13; Orofaciodigital syndrome XVIAR

Manifestation: Craniofacial; Musculoskeletal; Neurologic; Renal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 26123494; 26518474; 26595381

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMEM107 variants in ClinVar

9 Conditions Cataloged

not providedTotal: 80

Inborn genetic diseasesTotal: 20

not specifiedTotal: 9

TMEM107-related disorderTotal: 8

Meckel syndrome 13Total: 5

Orofaciodigital syndrome 16Total: 4

Leukoencephalopathy with calcifications and cystsTotal: 1

Joubert syndrome 29Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_183065.4. 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				23 clinvar	2 clinvar	25
missense	1 clinvar		41 clinvar	1 clinvar		43
nonsense	1 clinvar		3 clinvar			4
start loss						0
frameshift	3 clinvar	1 clinvar				4
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	1 clinvar			3
Total	6	2	45	24	2	79

Highest pathogenic variant AF is 0.000024163808

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_183065.4	RefSeq	NP_898888.1	5	MANE Select
ENST00000437139.7	Ensembl	ENSP00000402732.2	5	MANE Select
NM_001351278.2	RefSeq	NP_001338207.1	5	Standard
NM_001351279.2	RefSeq	NP_001338208.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

neural tube patterning
embryonic digit morphogenesis
cilium assembly
protein localization to ciliary transition zone
non-motile cilium assembly

Molecular Function

molecular_function
protein binding

Cellular Component

integral component of membrane
ciliary transition zone
MKS complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000316425
Coding exons: 5
Length: 3163
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	1.09	58	86.5	0.670	0.00000443	941
Missense (PolyPhen)		21	34.33	0.61172		389
Synonymous	0.681	32	37.3	0.858	0.00000211	307
Loss of Function	-0.906	10	7.35	1.36	3.12e-7	82

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000070	0.000070	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in cilia formation and embryonic patterning. Requires for normal Sonic hedgehog (Shh) signaling in the neural tube and acts in combination with GLI2 and GLI3 to pattern ventral and intermediate neuronal cell types (By similarity). During ciliogenesis regulates the ciliary transition zone localization of some MKS complex proteins (PubMed:26518474). {ECO:0000250|UniProtKB:Q9CPV0, ECO:0000269|PubMed:26518474}.;
Disease: DISEASE: Meckel syndrome 13 (MKS13) [MIM:617562]: A form of Meckel syndrome, a disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly. {ECO:0000269|PubMed:26123494, ECO:0000269|PubMed:26595381}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Orofaciodigital syndrome 16 (OFD16) [MIM:617563]: A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD16 features include postaxial polydactyly of the hands and feet, multiple tongue cysts, and dysmorphic features, including frontal narrowing, short palpebral fissures, flat nasal bridge, retrognathia, and low-set ears. Neurologic features include delayed psychomotor development and severe cognitive impairment. OFD16 inheritance is autosomal recessive. {ECO:0000269|PubMed:26518474, ECO:0000269|PubMed:26595381}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool: 0.515
RVIS EVS: -0.01
RVIS percentile EVS: 52.85

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.218

Gene Damage Prediction

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