CUX1

protein-coding

cut like homeobox 1, the group of CUT class homeoboxes and pseudogenes|Golgins

Gene summary

The protein encoded by this gene is a member of the homeodomain family of DNA binding proteins. It may regulate gene expression, morphogenesis, and differentiation and it may also play a role in the cell cycle progession. Several alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Feb 2011]

Previous symbols:

CUTL1

MANE transcript

NM_181552.4

Inheritance

ClinVar variants

P:52U:360B:133

Top phenotype

Global developmental delay with or without impaired intellectual development

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr7:101,815,904-102,283,958

External References & Databases

Ensembl (ENSG00000257923)

UniProt (P39880, Q13948)

Transcript & Mutation Effects

hg38 • Region Span ~468.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

global developmental delay with or without impaired intellectual developmentDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0032680

Submitter: Ambry Genetics

autosomal dominant non-syndromic intellectual disabilitySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015802

Submitter: Orphanet

global developmental delay with or without impaired intellectual developmentSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032680

Submitter: Labcorp Genetics (formerly Invitae)

global developmental delay with or without impaired intellectual developmentMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0032680

Submitter: G2P

Clinical Genomic Database (CGD)

Global developmental delay with or without impaired intellectual developmentAD

Manifestation: Neurologic

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: 30014507

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CUX1 variants in ClinVar

12 Conditions Cataloged

not providedTotal: 258

Inborn genetic diseasesTotal: 168

Global developmental delay with or without impaired intellectual developmentTotal: 98

not specifiedTotal: 65

CUX1-related disorderTotal: 41

Duane retraction syndromeTotal: 3

Neurodevelopmental disorderTotal: 2

See casesTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_181552.4. 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			3 clinvar	79 clinvar	7 clinvar	89
missense		2 clinvar	334 clinvar	46 clinvar	1 clinvar	383
nonsense	13 clinvar	12 clinvar	6 clinvar			31
start loss						0
frameshift	5 clinvar	14 clinvar	7 clinvar			26
splice donor/acceptor (+/-2bp)	1 clinvar	5 clinvar	10 clinvar			16
Total	19	33	360	125	8	545

Highest pathogenic variant AF is 0.000006571511

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 53 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_181552.4	RefSeq	NP_853530.2	24	MANE Select
ENST00000292535.12	Ensembl	ENSP00000292535.7	24	MANE Select
NM_001202543.2	RefSeq	NP_001189472.1	24	Standard
NM_001202544.3	RefSeq	NP_001189473.1	22	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Disease
Vesicle-mediated transport
Membrane Trafficking
Intra-Golgi traffic
Signaling by FGFR in disease

Biological Process

negative regulation of transcription by RNA polymerase II
retrograde transport, vesicle recycling within Golgi
regulation of transcription by RNA polymerase II
multicellular organism development
peptidyl-tyrosine phosphorylation

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
protein tyrosine kinase activity
protein binding, bridging
sequence-specific DNA binding

Cellular Component

Golgi membrane
nucleus
nucleoplasm
Golgi apparatus
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000360264
Coding exons: 24
Length: 468291
Individuals with no LoFs: 125737
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125748
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.75	543	851	0.638	0.0000572	9753
Missense (PolyPhen)		4	20.007	0.19993		283
Synonymous	-0.541	396	383	1.04	0.0000285	3009
Loss of Function	7.25	6	72.7	0.0825	0.00000367	824

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00016	0.00011	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in intra-Golgi retrograde transport. {ECO:0000269|PubMed:15718469}.;

Recessive Scores

pRec: 0.449

Intolerance Scores

LoFtool: 0.407
RVIS EVS: -1.87
RVIS percentile EVS: 2.01

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.783

Gene Damage Prediction

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