AKR1D1

aldo-keto reductase family 1 member D1, the group of Aldo-keto reductases

Basic information

Region (hg38): 7:138002323-138118305

Previous symbols: [ "SRD5B1" ]

Links

ENSG00000122787 ∙ NCBI:6718 ∙ OMIM:604741 ∙ HGNC:388 ∙ Uniprot:P51857 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital bile acid synthesis defect 2 (Definitive), mode of inheritance: AR
• congenital bile acid synthesis defect 2 (Strong), mode of inheritance: AR
• congenital bile acid synthesis defect 2 (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bile acid synthesis defect, congenital, 2	AR	Gastrointestinal	Early interventions, such as bile replacement therapy, can be beneficial, though liver transplant may be necessary in severe cases	Gastrointestinal	2897546; 3198770; 2072042; 2248502; 8707100; 12970144; 15030995; 20522910; 23160874

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AKR1D1 gene.

• Congenital bile acid synthesis defect 2 (2 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AKR1D1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	5	1	12
missense		4	50			54
nonsense	2	1				3
start loss						0
frameshift		2				2
inframe indel			2			2
splice donor/acceptor (+/-2bp)		5	1			6
splice region			2	5	3	10
non coding			50	12	34	96
Total	2	12	109	17	35

Highest pathogenic variant AF is 0.0000197

Variants in AKR1D1

This is a list of pathogenic ClinVar variants found in the AKR1D1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-138076493-T-G		Congenital bile acid synthesis defect 2	Uncertain significance (Jan 12, 2018)
7-138076528-A-G			Uncertain significance (Mar 11, 2015)
7-138076539-T-G		Congenital bile acid synthesis defect 2	Uncertain significance (Jan 13, 2018)
7-138076542-C-T		AKR1D1-related disorder	Conflicting classifications of pathogenicity (Oct 25, 2021)
7-138076566-C-T			Uncertain significance (Oct 06, 2017)
7-138076567-A-G		Inborn genetic diseases • AKR1D1-related disorder	Conflicting classifications of pathogenicity (Sep 21, 2023)
7-138076578-C-T		not specified	Conflicting classifications of pathogenicity (Jan 15, 2016)
7-138076581-CGGACTT-C		Congenital bile acid synthesis defect 2	Uncertain significance (Dec 04, 2020)
7-138076601-A-T		Inborn genetic diseases	Uncertain significance (Apr 28, 2022)
7-138076610-C-T			Uncertain significance (Jul 05, 2018)
7-138076612-G-T			Likely pathogenic (Feb 08, 2017)
7-138088545-T-G			Benign (Nov 10, 2018)
7-138088593-C-G			Uncertain significance (Oct 20, 2017)
7-138088607-A-G			Uncertain significance (Feb 27, 2022)
7-138088634-G-A			Uncertain significance (Jul 02, 2022)
7-138088634-G-T		Inborn genetic diseases	Uncertain significance (Sep 13, 2023)
7-138088640-A-G		Inborn genetic diseases	Uncertain significance (Jul 14, 2023)
7-138088655-C-T		Congenital bile acid synthesis defect 2	Pathogenic (May 08, 2023)
7-138088656-G-A			Uncertain significance (Aug 16, 2018)
7-138088664-G-A		Congenital bile acid synthesis defect 2	Uncertain significance (Jun 21, 2023)
7-138088679-T-C		AKR1D1-related disorder	Uncertain significance (Dec 28, 2022)
7-138088684-A-T		Inborn genetic diseases	Uncertain significance (Jun 11, 2021)
7-138088693-C-T		AKR1D1-related disorder	Likely benign (Sep 09, 2021)
7-138088694-G-A		Inborn genetic diseases	Uncertain significance (Sep 20, 2023)
7-138088702-G-A		Congenital bile acid synthesis defect 2	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AKR1D1	protein_coding	protein_coding	ENST00000242375	9	115663

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.72e-7	0.659	125694	0	54	125748	0.000215

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.172	175	182	0.964	0.00000985	2153
Missense in Polyphen		69	79.11	0.8722		955
Synonymous	-0.662	69	62.4	1.11	0.00000317	599
Loss of Function	1.15	13	18.3	0.709	9.50e-7	214

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000253	0.000239
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000329	0.000316
Middle Eastern	0.000109	0.000109
South Asian	0.000247	0.000229
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Efficiently catalyzes the reduction of progesterone, androstenedione, 17-alpha-hydroxyprogesterone and testosterone to 5-beta-reduced metabolites. The bile acid intermediates 7- alpha,12-alpha-dihydroxy-4-cholesten-3-one and 7-alpha-hydroxy-4- cholesten-3-one can also act as substrates. {ECO:0000269|PubMed:11342103}.
• Pathway: Steroid hormone biosynthesis - Homo sapiens (human);Primary bile acid biosynthesis - Homo sapiens (human);27-Hydroxylase Deficiency;17-Beta Hydroxysteroid Dehydrogenase III Deficiency;Bile Acid Biosynthesis;Steroidogenesis;Congenital Bile Acid Synthesis Defect Type II;Cerebrotendinous Xanthomatosis (CTX);Zellweger Syndrome;Familial Hypercholanemia (FHCA);Congenital Bile Acid Synthesis Defect Type III;Apparent mineralocorticoid excess syndrome;3-Beta-Hydroxysteroid Dehydrogenase Deficiency;21-hydroxylase deficiency (CYP21);Corticosterone methyl oxidase I deficiency (CMO I);Corticosterone methyl oxidase II deficiency - CMO II;Adrenal Hyperplasia Type 5 or Congenital Adrenal Hyperplasia due to 17 Alpha-hydroxylase Deficiency;Adrenal Hyperplasia Type 3 or Congenital Adrenal Hyperplasia due to 21-hydroxylase Deficiency;Congenital Lipoid Adrenal Hyperplasia (CLAH) or Lipoid CAH;Androgen and Estrogen Metabolism;17-alpha-hydroxylase deficiency (CYP17);Aromatase deficiency;11-beta-hydroxylase deficiency (CYP11B1);Metapathway biotransformation Phase I and II;Metabolism of lipids;Androgen and estrogen biosynthesis and metabolism;Metabolism;Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol;Synthesis of bile acids and bile salts via 24-hydroxycholesterol;Synthesis of bile acids and bile salts via 27-hydroxycholesterol;Synthesis of bile acids and bile salts;Bile acid and bile salt metabolism;Metabolism of steroids;Bile acid biosynthesis;C21-steroid hormone biosynthesis and metabolism;bile acid biosynthesis, neutral pathway (Consensus)

Recessive Scores

• pRec: 0.168

Intolerance Scores

• loftool: 0.937
• rvis_EVS: -0.65
• rvis_percentile_EVS: 16.36

Haploinsufficiency Scores

• pHI: 0.144
• hipred: N
• hipred_score: 0.353
• ghis: 0.476

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.943

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Akr1d1
• Phenotype: vision/eye phenotype

Gene ontology

• Biological process: bile acid biosynthetic process;cholesterol catabolic process;digestion;steroid metabolic process;C21-steroid hormone metabolic process;androgen metabolic process;bile acid catabolic process;oxidation-reduction process
• Cellular component: cytosol
• Molecular function: alditol:NADP+ 1-oxidoreductase activity;aldo-keto reductase (NADP) activity;steroid binding;alcohol dehydrogenase (NADP+) activity;steroid dehydrogenase activity;oxidoreductase activity;ketosteroid monooxygenase activity;delta4-3-oxosteroid 5beta-reductase activity