MISP

protein-coding

mitotic spindle positioning

Gene summary

The protein encoded by this gene is an actin-bundling protein involved in determining cell morphology and mitotic progression. The encoded protein is required for the proper positioning of the mitotic spindle. Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Feb 2016]

Previous symbols:

C19orf21

MANE transcript

NM_173481.4

Inheritance

—

ClinVar variants

U:197B:25

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.88

Max pathogenic AF

—

Genomic locus

chr19:751,112-764,318

External References & Databases

Ensembl (ENSG00000099812)

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

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MISP variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 200

not providedTotal: 11

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

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173481.4. 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	2 clinvar	4 clinvar	9
missense			190 clinvar	14 clinvar	5 clinvar	209
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	197	16	9	222

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_173481.4	RefSeq	NP_775752.1	4	MANE Select
ENST00000215582.8	Ensembl	ENSP00000215582.4	4	MANE Select
ENST00000871265.1	Ensembl	ENSP00000541324.1	4	Standard
ENST00000871265.2	Ensembl	ENSP00000541324.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell cycle
cell division

Molecular Function

actin binding

Cellular Component

cytoskeleton
plasma membrane
focal adhesion
cell cortex
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000215582
Coding exons: 4
Length: 13194
Individuals with no LoFs: 125621
Homozygous LoFs: 0
Heterozygous LoFs: 127
Defined: 125748
p: 0.000505

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.17	517	447	1.16	0.0000302	4315
Missense (PolyPhen)		150	124.08	1.2089		1248
Synonymous	-1.32	216	193	1.12	0.0000134	1448
Loss of Function	0.513	19	21.6	0.881	0.00000101	226

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00065	0.00062	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.00040	0.00040	rare
East Asian	0.000055	0.000054	rare
Finnish	0.00043	0.00037	rare
European (Non-Finnish)	0.00080	0.00077	rare
South Asian	0.00018	0.00016	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in mitotic spindle orientation and mitotic progression. Regulates the distribution of dynactin at the cell cortex in a PLK1-dependent manner, thus stabilizing cortical and astral microtubule attachments required for proper mitotic spindle positioning. May link microtubules to the actin cytospkeleton and focal adhesions. May be required for directed cell migration and centrosome orientation. May also be necessary for proper stacking of the Golgi apparatus. {ECO:0000269|PubMed:23509069, ECO:0000269|PubMed:23574715}.;

Intolerance Scores

RVIS EVS: -0.03
RVIS percentile EVS: 50.58

Essentials

Essential (CRISPR): N
Essential (gene trap): N

Gene Damage Prediction

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