TIMM44

protein-coding

translocase of inner mitochondrial membrane 44, the group of TIM23 complex

Gene summary

This gene encodes a peripheral membrane protein associated with the mitochondrial inner membrane translocase, which functions in the import of proteins across the mitochondrial inner membrane and into the mitochondrial matrix. The encoded protein mediates binding of mitochondrial heat shock protein 70 to the translocase of inner mitochondrial membrane 23 (TIM23) complex. Expression of this gene is upregulated in kidney in a mouse model of diabetes. A mutation in this gene is associated with familial oncocytic thyroid carcinoma. [provided by RefSeq, Jul 2016]

MANE transcript

NM_006351.4

Inheritance

ClinVar variants

U:90B:18

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.35

Max pathogenic AF

—

Genomic locus

chr19:7,926,718-7,943,667

External References & Databases

Ensembl (ENSG00000104980)

Transcript & Mutation Effects

hg38 • Region Span ~16.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

thyroid cancerLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0002108

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TIMM44 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 94

not providedTotal: 19

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006351.4. 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			4 clinvar	2 clinvar	9 clinvar	15
missense			82 clinvar	5 clinvar	2 clinvar	89
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	90	7	11	108

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006351.4	RefSeq	NP_006342.2	13	MANE Select
ENST00000270538.8	Ensembl	ENSP00000270538.2	13	MANE Select
ENST00000595565.5	Ensembl	ENSP00000469273.1	4	Standard
ENST00000595831.5	Ensembl	ENSP00000472916.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of proteins
Mitochondrial protein import

Biological Process

protein targeting to mitochondrion
protein import into mitochondrial matrix

Molecular Function

protein binding
ATP binding
chaperone binding

Cellular Component

mitochondrion
mitochondrial inner membrane
mitochondrial matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000270538
Coding exons: 13
Length: 17203
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	0.232	267	278	0.961	0.0000200	2935
Missense (PolyPhen)		38	51.359	0.7399		538
Synonymous	-0.503	128	121	1.06	0.00000985	852
Loss of Function	3.20	10	28.4	0.352	0.00000171	298

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.000099	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Essential component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner. Recruits mitochondrial HSP70 to drive protein translocation into the matrix using ATP as an energy source. {ECO:0000250|UniProtKB:Q01852}.;

Recessive Scores

pRec: 0.180

Intolerance Scores

LoFtool: 0.522
RVIS EVS: 0.09
RVIS percentile EVS: 60.65

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.991

Gene Damage Prediction

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