UHMK1

protein-coding

U2AF homology motif kinase 1, the group of RNA binding motif containing

Gene summary

The gene encodes a serine/threonine protein kinase that promotes cell cycle progression through G1 by phosphorylation of the cyclin-dependent kinase inhibitor 1B (p27Kip1), which causes nuclear export and degradation. The encoded protein is also thought to function in the adult nervous system and the gene has been associated with schizophrenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

MANE transcript

NM_175866.5

Inheritance

—

ClinVar variants

P:1U:57B:1

Top phenotype

Cerebral visual impairment and intellectual disability

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chr1:162,497,251-162,529,631

External References & Databases

Ensembl (ENSG00000152332)

Transcript & Mutation Effects

hg38 • Region Span ~32.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to UHMK1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 48

not providedTotal: 1

Cerebral visual impairment and intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_175866.5. 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	1 clinvar		3
missense		1 clinvar	52 clinvar			53
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	1	57	1	0	59

Highest pathogenic variant AF is 0.0000020521773

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_175866.5	RefSeq	NP_787062.1	8	MANE Select
ENST00000489294.2	Ensembl	ENSP00000420270.1	8	MANE Select
NM_001184763.1	RefSeq	NP_001171692.1	8	Standard
NM_144624.2	RefSeq	NP_653225.2	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell cycle arrest
peptidyl-serine phosphorylation
neuron projection development
positive regulation of translational initiation
protein autophosphorylation

Molecular Function

RNA binding
protein serine/threonine kinase activity
protein binding
ATP binding
transferase activity

Cellular Component

nucleus
nucleoplasm
cytoplasm
Golgi apparatus
axon

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000489294
Coding exons: 8
Length: 32379
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125748
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.844	196	232	0.844	0.0000111	2728
Missense (PolyPhen)		43	72.635	0.592		915
Synonymous	-2.26	118	90.6	1.30	0.00000453	829
Loss of Function	3.41	3	19.1	0.157	8.91e-7	237

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000054	0.000053	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Upon serum stimulation, phosphorylates CDKN1B/p27Kip1, thus controlling CDKN1B subcellular location and cell cycle progression in G1 phase. May be involved in trafficking and/or processing of RNA (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.511

Intolerance Scores

LoFtool: 0.597
RVIS EVS: -0.27
RVIS percentile EVS: 34.32

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.732

Gene Damage Prediction

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