SEPHS1

protein-coding

selenophosphate synthetase 1

Gene summary

This gene encodes an enzyme that synthesizes selenophosphate from selenide and ATP. Selenophosphate is the selenium donor used to synthesize selenocysteine, which is co-translationally incorporated into selenoproteins at in-frame UGA codons. [provided by RefSeq, Sep 2010]

MANE transcript

NM_012247.5

Inheritance

ClinVar variants

P:4U:48B:6

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chr10:13,317,428-13,348,298

External References & Databases

Ensembl (ENSG00000086475)

Transcript & Mutation Effects

hg38 • Region Span ~30.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: G2P

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SEPHS1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 31

not providedTotal: 22

Ververi-Brady syndrome 2Total: 4

SEPHS1-related disorderTotal: 1

SEPHS1-related developmental delayTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012247.5. 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				6 clinvar		6
missense	2 clinvar	2 clinvar	44 clinvar			48
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	2	2	48	6	0	58

Highest pathogenic variant AF is 0.0000065717704

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 54 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012247.5	RefSeq	NP_036379.2	8	MANE Select
ENST00000327347.10	Ensembl	ENSP00000367893.3	8	MANE Select
NM_001195602.2	RefSeq	NP_001182531.1	7	Standard
NM_001195604.2	RefSeq	NP_001182533.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Selenocompound metabolism - Homo sapiens (human)
selenocysteine biosynthesis

Biological Process

selenium compound metabolic process
cellular protein modification process
selenocysteine biosynthetic process
phosphorylation
tRNA seleno-modification

Molecular Function

selenide, water dikinase activity
protein binding
ATP binding
GTP binding
identical protein binding

Cellular Component

cytoplasm
plasma membrane
nuclear membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000327347
Coding exons: 8
Length: 30874
Individuals with no LoFs: 125743
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125745
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.24	99	240	0.412	0.0000139	2583
Missense (PolyPhen)		20	70.661	0.28304		779
Synonymous	-0.781	107	97.2	1.10	0.00000686	763
Loss of Function	3.46	1	15.9	0.0629	6.76e-7	190

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Synthesizes selenophosphate from selenide and ATP. {ECO:0000269|PubMed:7665581}.;

Recessive Scores

pRec: 0.136

Intolerance Scores

RVIS EVS: -0.65
RVIS percentile EVS: 16.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.990

Gene Damage Prediction

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