CLIP1

protein-coding

CAP-Gly domain containing linker protein 1

Gene summary

The protein encoded by this gene links endocytic vesicles to microtubules. This gene is highly expressed in Reed-Sternberg cells of Hodgkin disease. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

Previous symbols:

MANE transcript

NM_001247997.2

Inheritance

ClinVar variants

P:1U:188B:40

Top phenotype

autosomal recessive non-syndromic intellectual disability

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr12:122,271,432-122,422,669

External References & Databases

Ensembl (ENSG00000130779)

Transcript & Mutation Effects

hg38 • Region Span ~151.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal recessive non-syndromic intellectual disabilitySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019502

Submitter: Orphanet

intellectual disabilityLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0001071

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CLIP1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 184

not providedTotal: 27

CLIP1-related disorderTotal: 7

CLIP1-related intellectual disabilityTotal: 3

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

Short statureTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001247997.2. 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	22 clinvar	6 clinvar	32
missense			166 clinvar	12 clinvar		178
nonsense	1 clinvar		3 clinvar			4
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			14 clinvar			14
Total	1	0	188	34	6	229

Highest pathogenic variant AF is 0.0000037181264

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 81 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001247997.2	RefSeq	NP_001234926.1	25	MANE Select
ENST00000620786.5	Ensembl	ENSP00000479322.1	25	MANE Select
NM_001389291.1	RefSeq	NP_001376220.1	24	Standard
NM_002956.3	RefSeq	NP_002947.1	24	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
clip1a	Danio rerio	Structure: epiboly involved in gastrulation with mouth forming second Quality: delayed abnormal

Gene / Model

Organism

Observed Phenotype

clip1a

Danio rerio

Structure: epiboly involved in gastrulation with mouth forming second

Quality: delayed

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

mTOR signaling pathway - Homo sapiens (human)
Regulation of Microtubule Cytoskeleton
Signal Transduction
lissencephaly gene (lis1) in neuronal migration and development
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal

Biological Process

mitotic cell cycle
microtubule bundle formation
positive regulation of microtubule polymerization
protein transport into plasma membrane raft

Molecular Function

protein binding
microtubule binding
zinc ion binding
tubulin binding
protein homodimerization activity

Cellular Component

kinetochore
ruffle
nuclear envelope
endosome
centrosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000540338
Coding exons: 25
Length: 151201
Individuals with no LoFs: 125606
Homozygous LoFs: 0
Heterozygous LoFs: 142
Defined: 125748
p: 0.000565

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.08	589	749	0.787	0.0000409	9488
Missense (PolyPhen)		313	442.01	0.70813		5691
Synonymous	-0.944	314	293	1.07	0.0000176	2650
Loss of Function	6.07	15	69.7	0.215	0.00000356	920

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00060	0.00049	rare
Ashkenazi Jewish	0.0025	0.0020	notable
East Asian	0.00033	0.00033	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00057	0.00055	rare
South Asian	0.00094	0.00075	rare
Other	0.0013	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds to the plus end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes microtubule growth and microtubule bundling. Links cytoplasmic vesicles to microtubules and thereby plays an important role in intracellular vesicle trafficking. Plays a role macropinocytosis and endosome trafficking. {ECO:0000269|PubMed:12433698, ECO:0000269|PubMed:17563362, ECO:0000269|PubMed:17889670}.;

Recessive Scores

pRec: 0.323

Intolerance Scores

LoFtool: 0.729
RVIS EVS: -1.1
RVIS percentile EVS: 6.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.797

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High