MTCL1

protein-coding

microtubule crosslinking factor 1

Gene summary

Enables microtubule binding activity. Involved in chromosome segregation. Located in kinetochore; midbody; and spindle. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

KIAA0802
CCDC165
SOGA2

MANE transcript

NM_001395333.1

Inheritance

ClinVar variants

P:1U:309B:53

Top phenotype

hereditary neurological disease

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr18:8,705,556-8,832,778

External References & Databases

Ensembl (ENSG00000168502)

Transcript & Mutation Effects

hg38 • Region Span ~127.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cerebellar ataxiaLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0000437

Submitter: LiferaOmics

Genetic evidence – Published PMID: 30548255 – Reports one affected individual. Family 1 – one proband. Case-level (biallelic predicted null in AR model; homozygous; consanguinity not reported so no deduction applied) = 1.5; Segregation = 0; Case-control = 0 Family 1 total = 1.5 PMID: 30548255 total = 1.5 PMID: 32961396 – Reports one affected individual. Case-level (biallelic predicted null in AR model; homozygous; consanguinity −0.5 applied) = 1.0; Segregation = 0; Case-control = 0 Family 2 total = 1.0 PMID: 32961396 total = 1. Published genetic evidence total = 2.5 / 12 Genetic evidence – Our Cases Family 1 – one proband. Case-level (biallelic predicted null in AR model; homozygous; consanguinity −0.5 applied) = 1.0; Segregation = 0; Case-control = 0 Family 1 total = 1.0 Our Cases Total = 1.0 / 12 Updated Total Genetic Evidence (Published + Our Cases) Published genetic evidence: 2.5 Our additional cases: 1.0 Updated genetic total = 3.5 Experimental Evidence – Published Evidence supporting biological plausibility: MTCL1 is a microtubule-associated factor important in Purkinje neuron biology; disruption in model/functional studies supports a cerebellar mechanism relevant to ataxia. Gene function / biological plausibility = 0.5 Animal/model evidence (Purkinje neuron / motor coordination relevance) = 2.0 Experimental evidence total = 2.5 / 6 Updated Overall Score Genetic evidence = 3.5 Experimental evidence = 2.5 Updated total = 6.0 / 18

hereditary neurological diseaseSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0100545

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MTCL1 variants in ClinVar

6 Conditions Cataloged

Inborn genetic diseasesTotal: 334

not providedTotal: 23

not specifiedTotal: 4

Cerebellar ataxiaTotal: 2

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Autosomal dominant cerebellar ataxiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001395333.1. 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	7 clinvar	3 clinvar	12
missense			305 clinvar	40 clinvar	3 clinvar	348
nonsense	1 clinvar					1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	0	309	47	6	363

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 57 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001395333.1	RefSeq	NP_001382262.1	15	MANE Select
ENST00000695636.1	Ensembl	ENSP00000512073.1	15	MANE Select
NM_001378205.1	RefSeq	NP_001365134.1	14	Standard
NM_001378206.1	RefSeq	NP_001365135.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

microtubule bundle formation
regulation of autophagy
establishment or maintenance of epithelial cell apical/basal polarity
positive regulation of protein targeting to membrane
positive regulation of microtubule motor activity

Molecular Function

RNA binding
microtubule binding
protein homodimerization activity

Cellular Component

spindle pole
extracellular space
cytoplasm
cytoskeleton
apical plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000359865
Coding exons: 14
Length: 127118
Individuals with no LoFs: 125697
Homozygous LoFs: 0
Heterozygous LoFs: 51
Defined: 125748
p: 0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.610	1043	989	1.05	0.0000664	10304
Missense (PolyPhen)		349	362.7	0.96223		3892
Synonymous	-1.45	462	424	1.09	0.0000291	3204
Loss of Function	5.16	20	64.8	0.309	0.00000373	702

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00020	0.00018	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00029	0.00028	rare
South Asian	0.00024	0.00023	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Microtubule-associated factor involved in the late phase of epithelial polarization and microtubule dynamics regulation. Plays a role in the development and maintenance of non-centrosomal microtubule bundles at the lateral membrane in polarized epithelial cells. {ECO:0000269|PubMed:23902687}.;

Recessive Scores

pRec: 0.100

Intolerance Scores

RVIS EVS: -1.3
RVIS percentile EVS: 4.97

Essentials

Essential (gene trap): N