NIN

protein-coding

ninein, the group of EF-hand domain containing

Gene summary

This gene encodes one of the proteins important for centrosomal function. This protein is important for positioning and anchoring the microtubules minus-ends in epithelial cells. Localization of this protein to the centrosome requires three leucine zippers in the central coiled-coil domain. Multiple alternatively spliced transcript variants that encode different isoforms have been reported. [provided by RefSeq, Jul 2008]

MANE transcript

NM_020921.4

Inheritance

ClinVar variants

P:7U:634B:243

Top phenotype

Seckel syndrome 7

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr14:50,719,763-50,831,162

External References & Databases

Ensembl (ENSG00000100503)

Transcript & Mutation Effects

hg38 • Region Span ~111.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Seckel syndrome 7LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0013922

Submitter: PanelApp Australia

Seckel syndrome 7LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0013922

Submitter: Labcorp Genetics (formerly Invitae)

Seckel syndrome 7LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0013922

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Seckel syndrome 7AR

Manifestation: Craniofacial; Endocrine; Musculoskeletal; Neurologic

Intervention: Endocrine

Rationale: The condition can include manifestations including endocrine anomalies (eg, hypothyroidism, hypogonadism), some of which may respond to appropriate hormonal therapy (eg, thyroid hormone replacemetn therapy, estrogen therapy)

Refs: 22933543

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NIN variants in ClinVar

6 Conditions Cataloged

not providedTotal: 804

not specifiedTotal: 371

NIN-related disorderTotal: 31

Seckel syndrome 7Total: 22

Seckel syndromeTotal: 3

Joubert syndrome 3Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020921.4. 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			8 clinvar	179 clinvar	10 clinvar	197
missense			591 clinvar	43 clinvar	11 clinvar	645
nonsense		3 clinvar	15 clinvar			18
start loss						0
frameshift	3 clinvar	1 clinvar	14 clinvar			18
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	3	4	634	222	21	884

Highest pathogenic variant AF is 0.000024627408

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 66 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020921.4	RefSeq	NP_065972.4	29	MANE Select
ENST00000530997.7	Ensembl	ENSP00000436092.2	29	MANE Select
NM_016350.5	RefSeq	NP_057434.4	27	Standard
NM_182944.3	RefSeq	NP_891989.3	28	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
nin	Danio rerio	Structure: otolith Quality: decreased size abnormal

Gene / Model

Organism

Observed Phenotype

nin

Danio rerio

Structure: otolith

Quality: decreased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein localization
centriole-centriole cohesion
corpus callosum morphogenesis
corticospinal tract morphogenesis
positive regulation of microtubule polymerization

Molecular Function

calcium ion binding
protein binding
GTP binding
kinase binding

Cellular Component

pericentriolar material
spindle pole
nucleus
nucleolus
centrosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000382041
Coding exons: 28
Length: 111359
Individuals with no LoFs: 125652
Homozygous LoFs: 1
Heterozygous LoFs: 95
Defined: 125748
p: 0.000382

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.330	1049	1.08e+3	0.972	0.0000589	13881
Missense (PolyPhen)		300	349.41	0.85858		4897
Synonymous	1.02	390	417	0.936	0.0000233	3730
Loss of Function	6.59	36	111	0.325	0.00000588	1317

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00032	0.00029	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00033	0.00033	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00050	0.00049	rare
South Asian	0.00046	0.00046	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Centrosomal protein required in the positioning and anchorage of the microtubule minus-end in epithelial cells (PubMed:15190203, PubMed:23386061). May also act as a centrosome maturation factor (PubMed:11956314). May play a role in microtubule nucleation, by recruiting the gamma-tubulin ring complex to the centrosome (PubMed:15190203). Overexpression does not perturb nucleation or elongation of microtubules but suppresses release of microtubules (PubMed:15190203). Required for centriole organization and microtubule anchoring at the mother centriole (PubMed:23386061). {ECO:0000269|PubMed:11956314, ECO:0000269|PubMed:15190203, ECO:0000269|PubMed:23386061}.;
Disease: DISEASE: Seckel syndrome 7 (SCKL7) [MIM:614851]: A rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and mental retardation. {ECO:0000269|PubMed:22933543}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.175

Intolerance Scores

LoFtool: 0.943
RVIS EVS: 0.07
RVIS percentile EVS: 59.05

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.534

Gene Damage Prediction

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