KIF12

protein-coding

kinesin family member 12, the group of Kinesins

Gene summary

This gene encodes a member of the kinesin superfamily of microtubule-associated molecular motors with functions related to the microtubule cytosekelton. Members of this superfamily play important roles in intracellular transport and cell division. A similar protein in mouse functions in the beta cell antioxidant signaling cascade, acting as a scaffold for the transcription factor specificity protein 1 (Sp1). Mice that lack this gene exhibit beta cell oxidative stress resulting in hypoinsulinemic glucose intolerance. [provided by RefSeq, Jul 2016]

MANE transcript

NM_001388308.1

Inheritance

ClinVar variants

P:15U:109B:39

Top phenotype

Cholestasis, progressive familial intrahepatic, 8

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr9:114,086,126-114,099,292

External References & Databases

Ensembl (ENSG00000136883)

Transcript & Mutation Effects

hg38 • Region Span ~13.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cholestasis, progressive familial intrahepatic, 8STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030505

Submitter: PanelApp Australia

cholestasis, progressive familial intrahepatic, 8MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0030505

Submitter: Ambry Genetics

cholestasis, progressive familial intrahepatic, 8STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030505

Submitter: Labcorp Genetics (formerly Invitae)

cholestasisDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0001751

Submitter: King Faisal Specialist Hospital and Research Center

KIF12 was first reported in relation to autosomal recessive cholestasis in 2019 (Maddirevula S, et al., 2019, PMID: 30250217). At least 5 unique variants (e.g. missense and nonsense) have been reported in humans. Variants in this gene have been reported in at least 9 probands in 4 publications (PMID: 30250217; PMID: 30976738; PMID: 33456446; PMID: 31130284). Mice model of Kif12 modulates biliary phenotype severity, including cholangitis, and cystic kidney disease (PMID: 15728779). Kif12 expression in the liver tissues (PMID: 15728779) (No convincing contradictory evidence has emerged. Two publications with convincing evidence and no convincing contradictory evidence classified KIF12 as definitive. Gene is scored according to ClinGen classification.

Clinical Genomic Database (CGD)

Cholestasis, progressive familial intrahepatic, 8AR

Manifestation: Gastrointestinal

Intervention: Gastrointestinal

Rationale: Medical management may be beneficial as pertains to cholestasis and related sequelae; Liver transplant has been described

Refs: 30250217; 30976738; 34555379

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KIF12 variants in ClinVar

6 Conditions Cataloged

Inborn genetic diseasesTotal: 98

not providedTotal: 69

Cholestasis, progressive familial intrahepatic, 8Total: 18

KIF12-related disorderTotal: 18

not specifiedTotal: 7

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001388308.1. 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	18 clinvar	3 clinvar	23
missense		2 clinvar	102 clinvar	11 clinvar	7 clinvar	122
nonsense	3 clinvar	2 clinvar	1 clinvar			6
start loss						0
frameshift	2 clinvar	3 clinvar	3 clinvar			8
splice donor/acceptor (+/-2bp)		3 clinvar	1 clinvar			4
Total	5	10	109	29	10	163

Highest pathogenic variant AF is 0.000026256072

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001388308.1	RefSeq	NP_001375237.1	19	MANE Select
ENST00000640217.2	Ensembl	ENSP00000491702.1	19	MANE Select
NM_138424.2	RefSeq	NP_612433.1	14	Standard
ENST00000473174.1	Ensembl	ENSP00000491357.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vesicle-mediated transport
Membrane Trafficking
Kinesins
Factors involved in megakaryocyte development and platelet production
Hemostasis

Biological Process

microtubule-based movement
biological_process

Molecular Function

molecular_function
microtubule motor activity
ATP binding
microtubule binding
ATPase activity

Cellular Component

cytoplasm
kinesin complex
microtubule
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000374118
Coding exons: 14
Length: 13102
Individuals with no LoFs: 125707
Homozygous LoFs: 0
Heterozygous LoFs: 41
Defined: 125748
p: 0.000163

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.656	276	308	0.895	0.0000185	3228
Missense (PolyPhen)		78	93.933	0.83038		1033
Synonymous	0.343	115	120	0.960	0.00000613	1095
Loss of Function	1.70	23	33.6	0.684	0.00000217	300

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0.00011	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.000099	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0995

Intolerance Scores

LoFtool: 0.616
RVIS EVS: -0.13
RVIS percentile EVS: 43.98

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.143

Gene Damage Prediction

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