Gene Details | GeDiPNet - Complete Gene Info, Disease Associations & Pathways

Gene Gene information from NCBI Gene database. Gene SNPs Other IDs Associated diseases
Entrez ID	8659
Gene name	Aldehyde dehydrogenase 4 family member A1
Gene symbol	ALDH4A1
Synonyms (NCBI Gene)	ALDH4P5CDP5CDh
Chromosome	1
Chromosome location	1p36.13
Summary	This protein belongs to the aldehyde dehydrogenase family of proteins. This enzyme is a mitochondrial matrix NAD-dependent dehydrogenase which catalyzes the second step of the proline degradation pathway, converting pyrroline-5-carboxylate to glutamate. D

Show/Hide all (6)

SNP ID	Visualize variation	Clinical significance	Consequence
rs78532707	C>A,G,T	Conflicting-interpretations-of-pathogenicity	Splice donor variant, intron variant
rs137852937	G>A,C	Pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs149414160	A>G	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Intron variant, missense variant, coding sequence variant, non coding transcript variant
rs387906314	C>-	Likely-pathogenic	Genic upstream transcript variant, frameshift variant, coding sequence variant, non coding transcript variant
rs779536510	->A	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs1557620472	C>G	Likely-pathogenic	Splice acceptor variant

168

Show/Hide all (168)

miRTarBase ID	miRNA	Experiments	Reference
MIRT022075	hsa-miR-128-3p	Microarray	17612493
MIRT777420	hsa-miR-125a-5p	CLIP-seq
MIRT777421	hsa-miR-125b	CLIP-seq
MIRT777422	hsa-miR-128	CLIP-seq
MIRT777423	hsa-miR-183	CLIP-seq
MIRT777424	hsa-miR-2355-5p	CLIP-seq
MIRT777425	hsa-miR-3154	CLIP-seq
MIRT777426	hsa-miR-3179	CLIP-seq
MIRT777427	hsa-miR-3185	CLIP-seq
MIRT777428	hsa-miR-3653	CLIP-seq
MIRT777429	hsa-miR-3670	CLIP-seq
MIRT777430	hsa-miR-3679-3p	CLIP-seq
MIRT777431	hsa-miR-3714	CLIP-seq
MIRT777432	hsa-miR-3936	CLIP-seq
MIRT777433	hsa-miR-3940-3p	CLIP-seq
MIRT777434	hsa-miR-4252	CLIP-seq
MIRT777435	hsa-miR-4269	CLIP-seq
MIRT777436	hsa-miR-4319	CLIP-seq
MIRT777437	hsa-miR-4645-5p	CLIP-seq
MIRT777438	hsa-miR-4651	CLIP-seq
MIRT777439	hsa-miR-4663	CLIP-seq
MIRT777440	hsa-miR-4673	CLIP-seq
MIRT777441	hsa-miR-4722-3p	CLIP-seq
MIRT777442	hsa-miR-4726-3p	CLIP-seq
MIRT777443	hsa-miR-4732-3p	CLIP-seq
MIRT777444	hsa-miR-4733-3p	CLIP-seq
MIRT777445	hsa-miR-4755-3p	CLIP-seq
MIRT777446	hsa-miR-548an	CLIP-seq
MIRT777447	hsa-miR-589	CLIP-seq
MIRT777448	hsa-miR-608	CLIP-seq
MIRT777449	hsa-miR-670	CLIP-seq
MIRT777450	hsa-miR-1205	CLIP-seq
MIRT777451	hsa-miR-1537	CLIP-seq
MIRT777452	hsa-miR-1909	CLIP-seq
MIRT777453	hsa-miR-1976	CLIP-seq
MIRT777454	hsa-miR-3180-5p	CLIP-seq
MIRT777429	hsa-miR-3670	CLIP-seq
MIRT777439	hsa-miR-4663	CLIP-seq
MIRT777455	hsa-miR-520a-5p	CLIP-seq
MIRT777456	hsa-miR-525-5p	CLIP-seq
MIRT777457	hsa-miR-605	CLIP-seq
MIRT777458	hsa-miR-1913	CLIP-seq
MIRT777459	hsa-miR-1914	CLIP-seq
MIRT777460	hsa-miR-3145-5p	CLIP-seq
MIRT777461	hsa-miR-3153	CLIP-seq
MIRT777462	hsa-miR-324-3p	CLIP-seq
MIRT777463	hsa-miR-425	CLIP-seq
MIRT777464	hsa-miR-4313	CLIP-seq
MIRT777465	hsa-miR-4668-5p	CLIP-seq
MIRT777466	hsa-miR-4691-3p	CLIP-seq
MIRT777467	hsa-miR-4707-5p	CLIP-seq
MIRT777468	hsa-miR-4749-3p	CLIP-seq
MIRT777469	hsa-miR-508-5p	CLIP-seq
MIRT777470	hsa-miR-766	CLIP-seq
MIRT2170320	hsa-miR-1197	CLIP-seq
MIRT2170321	hsa-miR-1207-3p	CLIP-seq
MIRT2170322	hsa-miR-1207-5p	CLIP-seq
MIRT2170323	hsa-miR-122	CLIP-seq
MIRT2170324	hsa-miR-1226	CLIP-seq
MIRT2170325	hsa-miR-124	CLIP-seq
MIRT777420	hsa-miR-125a-5p	CLIP-seq
MIRT777421	hsa-miR-125b	CLIP-seq
MIRT777422	hsa-miR-128	CLIP-seq
MIRT2170326	hsa-miR-1294	CLIP-seq
MIRT2170327	hsa-miR-138	CLIP-seq
MIRT2170328	hsa-miR-149	CLIP-seq
MIRT2170329	hsa-miR-184	CLIP-seq
MIRT777459	hsa-miR-1914	CLIP-seq
MIRT2170330	hsa-miR-27a	CLIP-seq
MIRT2170331	hsa-miR-27b	CLIP-seq
MIRT2170332	hsa-miR-3064-3p	CLIP-seq
MIRT2170333	hsa-miR-3135b	CLIP-seq
MIRT777460	hsa-miR-3145-5p	CLIP-seq
MIRT777425	hsa-miR-3154	CLIP-seq
MIRT2170334	hsa-miR-3166	CLIP-seq
MIRT777426	hsa-miR-3179	CLIP-seq
MIRT2170335	hsa-miR-3184	CLIP-seq
MIRT777427	hsa-miR-3185	CLIP-seq
MIRT2170336	hsa-miR-3189-5p	CLIP-seq
MIRT2170337	hsa-miR-3200-5p	CLIP-seq
MIRT2170338	hsa-miR-3202	CLIP-seq
MIRT2170339	hsa-miR-3612	CLIP-seq
MIRT2170340	hsa-miR-3616-3p	CLIP-seq
MIRT2170341	hsa-miR-362-5p	CLIP-seq
MIRT2170342	hsa-miR-3652	CLIP-seq
MIRT2170343	hsa-miR-3672	CLIP-seq
MIRT2170344	hsa-miR-3677-5p	CLIP-seq
MIRT2170345	hsa-miR-3689a-3p	CLIP-seq
MIRT2170346	hsa-miR-3689c	CLIP-seq
MIRT2170347	hsa-miR-3689d	CLIP-seq
MIRT2170348	hsa-miR-3690	CLIP-seq
MIRT777431	hsa-miR-3714	CLIP-seq
MIRT2170349	hsa-miR-3910	CLIP-seq
MIRT2170350	hsa-miR-3921	CLIP-seq
MIRT2170351	hsa-miR-3922-5p	CLIP-seq
MIRT777432	hsa-miR-3936	CLIP-seq
MIRT777433	hsa-miR-3940-3p	CLIP-seq
MIRT2170352	hsa-miR-3944-5p	CLIP-seq
MIRT2170353	hsa-miR-423-5p	CLIP-seq
MIRT2170354	hsa-miR-4254	CLIP-seq
MIRT2170355	hsa-miR-4256	CLIP-seq
MIRT2170356	hsa-miR-4258	CLIP-seq
MIRT777435	hsa-miR-4269	CLIP-seq
MIRT2170357	hsa-miR-4280	CLIP-seq
MIRT777464	hsa-miR-4313	CLIP-seq
MIRT2170358	hsa-miR-4317	CLIP-seq
MIRT777436	hsa-miR-4319	CLIP-seq
MIRT2170359	hsa-miR-4324	CLIP-seq
MIRT2170360	hsa-miR-4329	CLIP-seq
MIRT2170361	hsa-miR-4430	CLIP-seq
MIRT2170362	hsa-miR-4459	CLIP-seq
MIRT2170363	hsa-miR-4463	CLIP-seq
MIRT2170364	hsa-miR-4481	CLIP-seq
MIRT2170365	hsa-miR-4492	CLIP-seq
MIRT2170366	hsa-miR-4498	CLIP-seq
MIRT2170367	hsa-miR-4505	CLIP-seq
MIRT2170368	hsa-miR-4511	CLIP-seq
MIRT2170369	hsa-miR-4533	CLIP-seq
MIRT2170370	hsa-miR-4641	CLIP-seq
MIRT2170371	hsa-miR-4642	CLIP-seq
MIRT2170372	hsa-miR-4648	CLIP-seq
MIRT2170373	hsa-miR-4650-5p	CLIP-seq
MIRT777438	hsa-miR-4651	CLIP-seq
MIRT2170374	hsa-miR-4653-5p	CLIP-seq
MIRT2170375	hsa-miR-4654	CLIP-seq
MIRT2170376	hsa-miR-4695-5p	CLIP-seq
MIRT2170377	hsa-miR-4708-3p	CLIP-seq
MIRT2170378	hsa-miR-4715-3p	CLIP-seq
MIRT2170379	hsa-miR-4722-5p	CLIP-seq
MIRT2170380	hsa-miR-4725-5p	CLIP-seq
MIRT2170381	hsa-miR-4728-3p	CLIP-seq
MIRT2170382	hsa-miR-4728-5p	CLIP-seq
MIRT2170383	hsa-miR-4738-5p	CLIP-seq
MIRT2170384	hsa-miR-4745-5p	CLIP-seq
MIRT2170385	hsa-miR-4753-5p	CLIP-seq
MIRT777445	hsa-miR-4755-3p	CLIP-seq
MIRT2170386	hsa-miR-4757-5p	CLIP-seq
MIRT2170387	hsa-miR-4758-3p	CLIP-seq
MIRT2170388	hsa-miR-4763-3p	CLIP-seq
MIRT2170389	hsa-miR-4769-5p	CLIP-seq
MIRT2170390	hsa-miR-4771	CLIP-seq
MIRT2170391	hsa-miR-4789-3p	CLIP-seq
MIRT2170392	hsa-miR-488	CLIP-seq
MIRT2170393	hsa-miR-500b	CLIP-seq
MIRT2170394	hsa-miR-504	CLIP-seq
MIRT2170395	hsa-miR-506	CLIP-seq
MIRT777469	hsa-miR-508-5p	CLIP-seq
MIRT2170396	hsa-miR-513a-5p	CLIP-seq
MIRT777446	hsa-miR-548an	CLIP-seq
MIRT2170397	hsa-miR-548b-3p	CLIP-seq
MIRT2170398	hsa-miR-548q	CLIP-seq
MIRT2170399	hsa-miR-592	CLIP-seq
MIRT2170400	hsa-miR-597	CLIP-seq
MIRT777457	hsa-miR-605	CLIP-seq
MIRT777448	hsa-miR-608	CLIP-seq
MIRT2170401	hsa-miR-615-5p	CLIP-seq
MIRT2170402	hsa-miR-619	CLIP-seq
MIRT2170403	hsa-miR-622	CLIP-seq
MIRT2170404	hsa-miR-628-5p	CLIP-seq
MIRT2170405	hsa-miR-634	CLIP-seq
MIRT2170406	hsa-miR-642b	CLIP-seq
MIRT2170407	hsa-miR-650	CLIP-seq
MIRT2170408	hsa-miR-662	CLIP-seq
MIRT2170409	hsa-miR-760	CLIP-seq
MIRT2170410	hsa-miR-762	CLIP-seq
MIRT777470	hsa-miR-766	CLIP-seq
MIRT2170411	hsa-miR-892b	CLIP-seq
MIRT2170412	hsa-miR-936	CLIP-seq

Show/Hide all (21)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003842	Function	L-glutamate gamma-semialdehyde dehydrogenase activity	IBA
GO:0003842	Function	L-glutamate gamma-semialdehyde dehydrogenase activity	IEA
GO:0003842	Function	L-glutamate gamma-semialdehyde dehydrogenase activity	TAS	8621661
GO:0004029	Function	Aldehyde dehydrogenase (NAD+) activity	IDA	4015840
GO:0004029	Function	Aldehyde dehydrogenase (NAD+) activity	TAS	8621661
GO:0005515	Function	Protein binding	IPI	32814053
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IDA
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005759	Component	Mitochondrial matrix	TAS	8621661
GO:0005829	Component	Cytosol	IDA
GO:0006560	Process	Proline metabolic process	IEA
GO:0006560	Process	Proline metabolic process	TAS	8621661
GO:0006562	Process	L-proline catabolic process	TAS	8621661
GO:0009055	Function	Electron transfer activity	TAS	8621661
GO:0010133	Process	L-proline catabolic process to L-glutamate	IEA
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0016620	Function	Oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor	IEA
GO:0019470	Process	Trans-4-hydroxy-L-proline catabolic process	TAS	21998747
GO:0042802	Function	Identical protein binding	IPI	22516612

MIM	HGNC	e!Ensembl
606811	406	ENSG00000159423

P30038

Protein name

Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial (P5C dehydrogenase) (EC 1.2.1.88) (Aldehyde dehydrogenase family 4 member A1) (L-glutamate gamma-semialdehyde dehydrogenase)

Protein function

Irreversible conversion of delta-1-pyrroline-5-carboxylate (P5C), derived either from proline or ornithine, to glutamate. This is a necessary step in the pathway interconnecting the urea and tricarboxylic acid cycles. The preferred substrate is

PDB

3V9G , 3V9H , 3V9I , 4OE5 , 8RKQ , 8RKR

Family and domains

Pfam

Accession	ID	Position in sequence	Description	Type
PF00171	Aldedh	74 → 547	Aldehyde dehydrogenase family	Family

Tissue specificity

TISSUE SPECIFICITY: Highest expression is found in liver followed by skeletal muscle, kidney, heart, brain, placenta, lung and pancreas.

Sequence

MLLPAPALRRALLSRPWTGAGLRWKHTSSLKVANEPVLAFTQGSPERDALQKALKDLKGR
MEAIPCVVGDEEVWTSDVQYQVSPFNHGHKVAKFCYADKSLLNKAIEAALAARKEWDLKP
IADRAQIFLKAADMLSGPRRAEILAKTMVGQGKTVIQAEIDAAAELIDFFRFNAKYAVEL
EGQQPISVPPSTNSTVYRGLEGFVAAISPFNFTAIGGNLAGAPALMGNVVLWKPSDTAML
ASYAVYRILREAGLPPNIIQFVPADGPLFGDTVTSSEHLCGINFTGSVPTFKHLWKQVAQ
NLDRFHTFPRLAGECGGKNFHFVHRSADVESVVSGTLRSAFEYGGQKCSACSRLYVPHSL
WPQIKGRLLEEHSRIKVGDPAEDFGTFFSAVIDAKSFARIKKWLEHARSSPSLTILAGGK
CDDSVGYFVEPCIVESKDPQEPIMKEEIFGPVLSVYVYPDDKYKETLQLVDSTTSYGLTG
AVFSQDKDVVQEATKVLRNAAGNFYINDKSTGSIVGQQPFGGARASGTNDKPGGPHYILR
WTSPQVIKETHKPLGDWSYAYMQ

Sequence length

563

Interactions

View interactions

Evidence Score: ★☆☆☆☆ Gene-disease association found in Text Mining only ★★☆☆☆ Found in Text Mining and Unknown/Other Associations ★★★☆☆ Reported in Unknown/Other Associations across ≥2 Sources ★★★★☆ ClinVar: Pathogenic/Likely Pathogenic (<5 Variants) ★★★★★ ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Show/Hide Causal Diseases (1)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Causal Diseases associated with Pathogenic or Likely Pathogenic variants in ClinVar
Hyperprolinemia type 2	Likely pathogenic; Pathogenic	rs756807746, rs2100593635, rs2522599015, rs779536510, rs387906314, rs2522617063, rs78532707, rs1557620472	RCV001808041 RCV002052047 RCV002481176 RCV000004209 RCV000004211 RCV003389279 RCV000505674 RCV000692385 View all (3 more)	★★★★★ ★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Show/Hide Unknown Diseases (14)

Phenotype Name	Clinical Significance	Source	Evidence Score
Unknown / Other Associations ClinVar entries with uncertain/conflicting evidence, and associations from other databases (OMIM, Orphanet, GWAS, etc.) where the gene is not established as causal.
ALDH4A1-related disorder	Likely benign; Benign; Conflicting classifications of pathogenicity	ClinVar	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ALZHEIMER DISEASE	—	GWAS catalog	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANOREXIA NERVOSA	—	GWAS catalog	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDER	—	CTD	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDERS	—	Disgenet	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EATING DISORDER	—	GWAS catalog	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hyperprolinemia	Uncertain significance; Likely benign	ClinVar Disgenet	★★★★★ ★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
HYPERPROLINEMIA, TYPE II	—	HPO	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intellectual disability	Conflicting classifications of pathogenicity; Uncertain significance; Likely benign	ClinVar Disgenet	★★★★★ ★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Melanoma	Benign	ClinVar	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-ALCOHOLIC FATTY LIVER DISEASE	—	CTD, Disgenet CTD, Disgenet	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NONALCOHOLIC STEATOHEPATITIS	—	Disgenet	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Uncertain significance	ClinVar	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Seizure	Uncertain significance	ClinVar	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Show/Hide Text Mining Associations (24)

Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Associations from Text Mining Disease associations identified through text mining
Bipolar Disorder	Bipolar disorder	Pubtator	32065947	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Cardiomyopathy Dilated	Dilated cardiomyopathy	Pubtator	27711126	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Fatty Liver Disease	Fatty Liver	BEFREE	29718361		★★★★★ ★☆☆☆☆ Found in Text Mining only
HYPERGLYCINURIA (disorder)	Hyperglycinuria	HPO_DG			★★★★★ ★☆☆☆☆ Found in Text Mining only
Hyperprolinemia	Hyperprolinemia	BEFREE	22516612		★★★★★ ★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Hyperprolinemia	Hyperprolinemia	HPO_DG			★★★★★ ★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Hyperprolinemia type 2	Hyperprolinemia	BEFREE	10971205, 16934832, 22516612		★★★★★ ★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hyperprolinemia type 2	Hyperprolinemia	CLINGEN_DG	13835167, 4369405, 9700195		★★★★★ ★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hyperprolinemia type 2	Hyperprolinemia	UNIPROT_DG	22516612, 9700195		★★★★★ ★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hyperprolinemia type 2	Hyperprolinemia	CTD_human_DG	25641190		★★★★★ ★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hyperprolinemia type 2	Hyperprolinemia	GENOMICS_ENGLAND_DG	27604308, 9700195		★★★★★ ★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hyperprolinemia type 2	Hyperprolinemia	Pubtator	31884946	Associate	★★★★★ ★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hyperprolinemia type 2	Hyperprolinemia	CLINVAR_DG	9700195		★★★★★ ★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hyperprolinemia type 2	Hyperprolinemia	ORPHANET_DG	9700195		★★★★★ ★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hyperprolinemia type 2	Hyperprolinemia	Orphanet			★★★★★ ★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Insulin Resistance	Diabetes mellitus, type 2	Pubtator	30678306	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	GENOMICS_ENGLAND_DG	27604308		★★★★★ ★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Intellectual Disability	Mental retardation	HPO_DG			★★★★★ ★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Nasopharyngeal Carcinoma	Nasopharyngeal carcinoma	Pubtator	34680942	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Non-alcoholic Fatty Liver Disease	Non-Alcoholic Fatty Liver Disease	CTD_human_DG	29718361		★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonalcoholic Steatohepatitis	Non-alcoholic Fatty Liver Disease	CTD_human_DG	29718361		★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prolinuria	Prolinuria	HPO_DG			★★★★★ ★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	Pubtator	32065947	Stimulate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Seizures	Seizures	Pubtator	31884946	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only

ALDH4A1 (aldehyde dehydrogenase 4 family member A1)