SEH1L

protein-coding

SEH1 like nucleoporin, the group of WD repeat domain containing|Nucleoporins|GATOR2 subcomplex

Gene summary

The protein encoded by this gene is part of a nuclear pore complex, Nup107-160. This protein contains WD repeats and shares 34% amino acid identity with yeast Seh1 and 30% identity with yeast Sec13. All constituents of the Nup107-160 complex, including this protein, specifically localize to kinetochores in mitosis. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001013437.2

Inheritance

—

ClinVar variants

U:55B:2

Top phenotype

Tooth agenesis

gnomAD constraint

pLI —, LoF o/e 0.26

Max pathogenic AF

—

Genomic locus

chr18:12,947,133-12,987,536

External References & Databases

Ensembl (ENSG00000085415)

Transcript & Mutation Effects

hg38 • Region Span ~40.4 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 SEH1L variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 48

not providedTotal: 1

Tooth agenesisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001013437.2. 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			1 clinvar	1 clinvar	1 clinvar	3
missense			52 clinvar			52
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	55	1	1	57

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001013437.2	RefSeq	NP_001013455.1	9	MANE Select
ENST00000399892.7	Ensembl	ENSP00000382779.1	9	MANE Select
NM_031216.4	RefSeq	NP_112493.2	9	Standard
ENST00000262124.15	Ensembl	ENSP00000262124.10	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

mTOR signaling pathway - Homo sapiens (human)
RNA transport - Homo sapiens (human)
tRNA processing
Disease
Signal Transduction

Biological Process

cytokine production involved in inflammatory response
mRNA export from nucleus
nuclear pore organization
mitotic metaphase plate congression
viral process

Molecular Function

protein binding

Cellular Component

kinetochore
condensed chromosome kinetochore
nuclear envelope
lysosomal membrane
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000399892
Coding exons: 9
Length: 40404
Individuals with no LoFs: 125718
Homozygous LoFs: 0
Heterozygous LoFs: 30
Defined: 125748
p: 0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.74	164	240	0.684	0.0000121	2765
Missense (PolyPhen)		31	70.196	0.44162		848
Synonymous	0.278	79	82.2	0.961	0.00000425	805
Loss of Function	3.33	6	23.4	0.257	0.00000135	240

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex is required for the assembly of a functional NPC. The Nup107-160 subcomplex is also required for normal kinetochore microtubule attachment, mitotic progression and chromosome segregation. This subunit plays a role in recruitment of the Nup107-160 subcomplex to the kinetochore. {ECO:0000269|PubMed:15146057, ECO:0000269|PubMed:17363900}.;

Recessive Scores

pRec: 0.137

Intolerance Scores

LoFtool: 0.380
RVIS EVS: -0.12
RVIS percentile EVS: 45.13

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.848

Gene Damage Prediction

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