AASDH

protein-coding

aminoadipate-semialdehyde dehydrogenase, the group of Acyl-CoA synthetase family

Gene summary

This gene encodes a member of the non-ribosome peptide syntesase (NRPS) enzyme family. The encoded protein contains an AMP-binding domain, PP-binding (phosphopantetheine, or pantetheine 4'phosphate-binding) domain and the Pyrrolo-quinoline quinon (PQQ) binding domain. The protein is expressed in several adult tissues. [provided by RefSeq, Apr 2016]

MANE transcript

NM_181806.4

Inheritance

—

ClinVar variants

U:139B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chr4:56,338,287-56,387,508

External References & Databases

Ensembl (ENSG00000157426)

Transcript & Mutation Effects

hg38 • Region Span ~49.2 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 AASDH variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 135

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_181806.4. 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	3 clinvar		6
missense			131 clinvar	8 clinvar		139
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	139	11	0	150

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 51 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_181806.4	RefSeq	NP_861522.2	14	MANE Select
ENST00000205214.11	Ensembl	ENSP00000205214.6	14	MANE Select
NM_001286668.2	RefSeq	NP_001273597.1	13	Standard
NM_001286669.2	RefSeq	NP_001273598.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

fatty acid metabolic process
beta-alanine metabolic process
amino acid activation for nonribosomal peptide biosynthetic process

Molecular Function

ATP binding
acid-thiol ligase activity

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000205214
Coding exons: 14
Length: 49211
Individuals with no LoFs: 125522
Homozygous LoFs: 0
Heterozygous LoFs: 225
Defined: 125747
p: 0.000895

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.255	534	551	0.969	0.0000263	7139
Missense (PolyPhen)		144	171.57	0.83929		2031
Synonymous	0.913	188	205	0.919	0.0000103	2124
Loss of Function	2.50	28	46.4	0.604	0.00000227	645

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00080	0.00080	rare
Latino/Admixed American	0.0016	0.0015	notable
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00078	0.00076	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.0010	0.0010	notable
South Asian	0.00050	0.00049	rare
Other	0.0010	0.00098	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Covalently binds beta-alanine in an ATP-dependent manner to form a thioester bond with its phosphopantetheine group and transfers it to an, as yet, unknown acceptor. May be required for a post-translational protein modification or for post- transcriptional modification of an RNA. {ECO:0000250|UniProtKB:Q80WC9}.;

Recessive Scores

pRec: 0.138

Intolerance Scores

LoFtool: 0.986
RVIS EVS: 1.05
RVIS percentile EVS: 91.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.801

Gene Damage Prediction

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