SLC45A1

protein-coding

solute carrier family 45 member 1, the group of Solute carrier family 45

Gene summary

This gene was isolated initially from a region on chromosome 1p that is frequently deleted in human neuroblastoma, although no causal relationship has since been demonstrated. The encoded protein belongs to the glycoside-pentoside-hexuronide cation symporter transporter family and may play a role in glucose uptake. [provided by RefSeq, Mar 2014]

Previous symbols:

DNB5

MANE transcript

NM_001080397.3

Inheritance

ClinVar variants

P:2U:142B:71

Top phenotype

Intellectual developmental disorder with neuropsychiatric features (IDDNPF)

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr1:8,318,114-8,344,167

External References & Databases

Ensembl (ENSG00000162426)

Transcript & Mutation Effects

hg38 • Region Span ~26.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder with neuropsychiatric featuresLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0044322

Submitter: Ambry Genetics

intellectual developmental disorder with neuropsychiatric featuresSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0044322

Submitter: Labcorp Genetics (formerly Invitae)

intellectual developmental disorder with neuropsychiatric featuresSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0044322

Submitter: G2P

autosomal recessive non-syndromic intellectual disabilitySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019502

Submitter: Orphanet

intellectual developmental disorder with neuropsychiatric featuresSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0044322

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Intellectual developmental disorder with neuropsychiatric features (IDDNPF)AR

Manifestation: Craniofacial; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 27431290; 28434495

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC45A1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 134

not providedTotal: 73

Intellectual developmental disorder with neuropsychiatric featuresTotal: 20

SLC45A1-related disorderTotal: 17

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001080397.3. 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	56 clinvar	6 clinvar	63
missense		2 clinvar	137 clinvar	9 clinvar		148
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	2	142	65	6	215

Highest pathogenic variant AF is 0.00009608911

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001080397.3	RefSeq	NP_001073866.3	8	MANE Select
ENST00000471889.7	Ensembl	ENSP00000418096.3	8	MANE Select
NM_001379614.1	RefSeq	NP_001366543.1	8	Standard
NM_001379615.1	RefSeq	NP_001366544.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

glucose transmembrane transport

Molecular Function

sucrose:proton symporter activity
symporter activity

Cellular Component

membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000471889
Coding exons: 8
Length: 26342
Individuals with no LoFs: 125647
Homozygous LoFs: 0
Heterozygous LoFs: 101
Defined: 125748
p: 0.000402

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.47	408	500	0.816	0.0000351	4808
Missense (PolyPhen)		151	214.42	0.70422		2191
Synonymous	-0.321	249	243	1.03	0.0000202	1625
Loss of Function	2.56	12	26.1	0.460	0.00000139	272

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0013	0.0012	notable
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00038	0.00038	rare
Finnish	0.00099	0.00097	rare
European (Non-Finnish)	0.00041	0.00040	rare
South Asian	0	0.0	absent
Other	0.00066	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Proton-associated glucose transporter in the brain. {ECO:0000250|UniProtKB:Q8K4S3, ECO:0000269|PubMed:28434495}.;

Recessive Scores

pRec: 0.116

Intolerance Scores

LoFtool: 0.184
RVIS EVS: -2.04
RVIS percentile EVS: 1.67

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.254

Gene Damage Prediction

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