CYB5RL

Summary

CYB5RL (cytochrome b5 reductase like, HGNC:32220) is a protein-coding gene on chromosome 1p32.3, encoding NADH-cytochrome b5 reductase-like (Q6IPT4). NADH-cytochrome b5 reductases are involved in desaturation and elongation of fatty acids, cholesterol biosynthesis, drug metabolism, and, in erythrocyte, methemoglobin reduction.

Predicted to enable cytochrome-b5 reductase activity, acting on NAD(P)H. Predicted to be involved in bicarbonate transport. Located in nucleoplasm.

Source: NCBI Gene 606495 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 60 total
• MANE Select transcript: NM_001031672

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32220
Approved symbol	CYB5RL
Name	cytochrome b5 reductase like
Location	1p32.3
Locus type	gene with protein product
Status	Approved
Aliases	LOC606495
Ensembl gene	ENSG00000215883
Ensembl biotype	protein_coding
Entrez	606495

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 11 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000287899, ENST00000420054, ENST00000421415, ENST00000462299, ENST00000490863, ENST00000493530, ENST00000497820, ENST00000528287, ENST00000534324, ENST00000886275, ENST00000886276, ENST00000886277, ENST00000886278, ENST00000913265, ENST00000963051, ENST00000963052

RefSeq mRNA: 4 — MANE Select: NM_001031672 NM_001031672, NM_001353353, NM_001353354, NM_001353356

CCDS: CCDS44151, CCDS85978

Canonical transcript exons

ENST00000534324 — 8 exons

Exon	Start	End
ENSE00001422839	54190748	54190896
ENSE00001682160	54169651	54174822
ENSE00003519273	54184161	54184265
ENSE00003632606	54179149	54179352
ENSE00003638048	54187652	54187739
ENSE00003656062	54196369	54196491
ENSE00003660608	54195419	54195715
ENSE00003920783	54199976	54200030

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 85.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.2507 / max 36.6681, expressed in 1244 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12452	2.2507	1244

Top tissues by expression

277 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	85.34	silver quality
olfactory bulb	UBERON:0002264	82.88	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.84	gold quality
cervix squamous epithelium	UBERON:0006922	79.46	silver quality
tendon of biceps brachii	UBERON:0008188	77.90	gold quality
hair follicle	UBERON:0002073	77.50	silver quality
diaphragm	UBERON:0001103	77.31	gold quality
gluteal muscle	UBERON:0002000	76.93	gold quality
ventricular zone	UBERON:0003053	76.81	gold quality
left adrenal gland cortex	UBERON:0035825	76.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.49	gold quality
right adrenal gland cortex	UBERON:0035827	76.49	gold quality
cervix epithelium	UBERON:0004801	76.38	silver quality
right adrenal gland	UBERON:0001233	76.23	gold quality
left adrenal gland	UBERON:0001234	76.17	gold quality
adrenal cortex	UBERON:0001235	76.17	gold quality
tongue squamous epithelium	UBERON:0006919	76.14	gold quality
adrenal gland	UBERON:0002369	75.20	gold quality
medial globus pallidus	UBERON:0002477	75.19	silver quality
body of pancreas	UBERON:0001150	75.00	gold quality
smooth muscle tissue	UBERON:0001135	74.93	gold quality
stromal cell of endometrium	CL:0002255	74.67	gold quality
buccal mucosa cell	CL:0002336	74.63	silver quality
parotid gland	UBERON:0001831	74.40	silver quality
pancreas	UBERON:0001264	74.31	gold quality
hindlimb stylopod muscle	UBERON:0004252	74.30	gold quality
pigmented layer of retina	UBERON:0001782	74.01	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	74.00	silver quality
secondary oocyte	CL:0000655	73.86	silver quality
ganglionic eminence	UBERON:0004023	73.85	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

67 targeting CYB5RL, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-128-1-5P	99.33	60.46	332
HSA-MIR-128-2-5P	99.33	60.83	311
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-100-3P	99.20	67.33	672

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cyb5rl	ENSMUSG00000028621
rattus_norvegicus	Cyb5rl	ENSRNOG00000009148
drosophila_melanogaster	CG7914	FBGN0030995

Paralogs (5): CYB5R4 (ENSG00000065615), CYB5R3 (ENSG00000100243), OXNAD1 (ENSG00000154814), CYB5R1 (ENSG00000159348), CYB5R2 (ENSG00000166394)

Protein

Protein identifiers

NADH-cytochrome b5 reductase-like — Q6IPT4 (reviewed: Q6IPT4)

All UniProt accessions (6): Q6IPT4, E9PL89, E9PMD3, F8VW03, F8WDU4, H0YDY7

UniProt curated annotations — full annotation on UniProt →

Function. NADH-cytochrome b5 reductases are involved in desaturation and elongation of fatty acids, cholesterol biosynthesis, drug metabolism, and, in erythrocyte, methemoglobin reduction.

Similarity. Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6IPT4-1	1	yes
Q6IPT4-3	2
Q6IPT4-4	3

RefSeq proteins (4): NP_001026842, NP_001340282, NP_001340283, NP_001340285 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001433	OxRdtase_FAD/NAD-bd	Domain
IPR001834	CBR-like	Family
IPR008333	Cbr1-like_FAD-bd_dom	Domain
IPR017927	FAD-bd_FR_type	Domain
IPR017938	Riboflavin_synthase-like_b-brl	Homologous_superfamily
IPR019180	Oxidoreductase-like_N	Domain
IPR039261	FNR_nucleotide-bd	Homologous_superfamily

Pfam: PF00175, PF00970, PF09791

Catalyzed reactions (Rhea), 1 shown:

• 2 Fe(III)-[cytochrome b5] + NADH = 2 Fe(II)-[cytochrome b5] + NAD(+) + H(+) (RHEA:46680)

UniProt features (10 total): domain 2, binding site 2, splice variant 2, sequence conflict 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6IPT4-F1	92.33	0.86

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (2): 157–172; 182–214

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1237044	Erythrocytes take up carbon dioxide and release oxygen
R-HSA-1480926	O2/CO2 exchange in erythrocytes
R-HSA-382551	Transport of small molecules

MSigDB gene sets: 63 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_BICARBONATE_TRANSPORT, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_NAD_P_H, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT, MULLIGHAN_NPM1_MUTATED_SIGNATURE_1_UP, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, DELACROIX_RARG_BOUND_MEF, DELACROIX_RAR_BOUND_ES, GOMF_CYTOCHROME_B5_REDUCTASE_ACTIVITY_ACTING_ON_NAD_P_H, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_NAD_P_H_HEME_PROTEIN_AS_ACCEPTOR, REACTOME_TRANSPORT_OF_SMALL_MOLECULES

GO Biological Process (1): bicarbonate transport (GO:0015701)

GO Molecular Function (3): cytochrome-b5 reductase activity, acting on NAD(P)H (GO:0004128), oxidoreductase activity (GO:0016491), cytochrome-b5 reductase activity, acting on NADH (GO:0090524)

GO Cellular Component (2): nucleoplasm (GO:0005654), endoplasmic reticulum membrane (GO:0005789)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
O2/CO2 exchange in erythrocytes	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	1
oxidoreductase activity, acting on NAD(P)H, heme protein as acceptor	1
catalytic activity	1
cytochrome-b5 reductase activity, acting on NAD(P)H	1
nuclear lumen	1
cellular anatomical structure	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1

Protein interactions and networks

STRING

1212 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYB5RL	CYB5B	O43169	994
CYB5RL	CYB5A	P00167	994
CYB5RL	SCD	O00767	822
CYB5RL	POR	P16435	663
CYB5RL	CYP51A1	Q16850	555
CYB5RL	DHODH	Q02127	528
CYB5RL	SUOX	P51687	489
CYB5RL	NQO1	P15559	448
CYB5RL	CYCS	P00001	433
CYB5RL	CYP27C1	Q4G0S4	425
CYB5RL	G6PD	P11413	419
CYB5RL	H6PD	O95479	408
CYB5RL	XDH	P47989	402
CYB5RL	MPI	P34949	394
CYB5RL	E7EVH7	E7EVH7	391

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A2AV36, A3KP77, A4IHY0, A8E7D2, B1AS42, D3ZG52, P00387, P17571, P20070, P32232, P35520, Q05B89, Q07G10, Q0CT94, Q13057, Q2UM43, Q3UZW7, Q4V7D6, Q4WN24, Q502I6, Q58DM7, Q58E95, Q58H57, Q5B5L3, Q5EB81, Q5R4D2, Q5RCH4, Q5U378, Q60HG4, Q6ING7, Q6IPT4, Q6JQN1, Q6ZQJ5, Q7T0L7, Q7T0X7, Q7T291, Q7ZW24, Q8AWD2, Q8K4Z3, Q8VE38

Diamond homologs: A0A286R227, A1C7E9, A1CRK9, A1D4H0, A1DHW1, A2Q898, A2QCV4, A3GF86, A3LT66, A4QR21, A4R935, A5DQ25, A5DQE4, A5E5C5, A5E7U2, A6R1T7, A6R2K7, A6SI59, A6ZVM6, A6ZZH2, A7EKT5, A7THS1, A7TM72, A7TNL7, B0CQN7, C8VJR5, O74557, P07514, P08509, P0CP14, P0CP15, P11605, P17570, P20070, P22945, P23312, P27783, P27967, P36060, P36841

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

60 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1485 predictions. Top by Δscore:

Variant	Effect	Δscore
1:54179348:CCATA:C	acceptor_gain	1.0000
1:54179349:CATAC:C	acceptor_gain	1.0000
1:54179351:TA:T	acceptor_gain	1.0000
1:54184266:C:CC	acceptor_gain	1.0000
1:54179143:GCTCA:G	donor_loss	0.9900
1:54179145:TCA:T	donor_loss	0.9900
1:54179146:CA:C	donor_loss	0.9900
1:54179147:ACC:A	donor_loss	0.9900
1:54179147:ACCTG:A	donor_loss	0.9900
1:54179148:C:CT	donor_loss	0.9900
1:54179148:CCTGG:C	donor_gain	0.9900
1:54179353:C:CC	acceptor_gain	0.9900
1:54184156:CTGA:C	donor_loss	0.9900
1:54184157:TGA:T	donor_loss	0.9900
1:54184158:GA:G	donor_loss	0.9900
1:54184159:A:C	donor_loss	0.9900
1:54184159:ACCTG:A	donor_loss	0.9900
1:54184160:C:A	donor_loss	0.9900
1:54184160:C:CA	donor_loss	0.9900
1:54184263:GCA:G	acceptor_gain	0.9900
1:54184263:GCAC:G	acceptor_loss	0.9900
1:54184264:CA:C	acceptor_gain	0.9900
1:54184264:CAC:C	acceptor_gain	0.9900
1:54184265:AC:A	acceptor_loss	0.9900
1:54184267:T:G	acceptor_loss	0.9900
1:54187736:CCCT:C	acceptor_gain	0.9900
1:54187737:CCTC:C	acceptor_gain	0.9900
1:54187738:CT:C	acceptor_gain	0.9900
1:54187740:C:CC	acceptor_gain	0.9900
1:54190732:CGCTA:C	donor_loss	0.9900

AlphaMissense

2067 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:54184198:C:G	R168P	0.969
1:54184202:A:G	W167R	0.968
1:54184202:A:T	W167R	0.968
1:54190864:G:C	F77L	0.948
1:54190864:G:T	F77L	0.948
1:54190866:A:G	F77L	0.948
1:54179255:A:T	V213D	0.947
1:54174622:G:C	F315L	0.945
1:54174622:G:T	F315L	0.945
1:54174624:A:G	F315L	0.945
1:54190757:A:G	L113P	0.944
1:54195473:C:A	W48C	0.938
1:54195473:C:G	W48C	0.938
1:54190804:A:C	F97L	0.932
1:54190804:A:T	F97L	0.932
1:54190806:A:G	F97L	0.932
1:54174685:G:C	F294L	0.925
1:54174685:G:T	F294L	0.925
1:54174687:A:G	F294L	0.925
1:54179342:A:G	L184P	0.924
1:54190805:A:G	F97S	0.924
1:54174704:A:T	V288D	0.923
1:54195475:A:G	W48R	0.919
1:54195475:A:T	W48R	0.919
1:54179182:G:C	F237L	0.917
1:54179182:G:T	F237L	0.917
1:54179184:A:G	F237L	0.917
1:54184196:C:G	G169R	0.915
1:54184196:C:T	G169R	0.915
1:54184234:A:T	V156D	0.908

dbSNP variants (sampled 300 via entrez): RS1000196634 (1:54180112 C>T), RS1000220694 (1:54197714 C>T), RS1000348010 (1:54172354 T>C), RS1000388670 (1:54186082 T>C), RS1000400768 (1:54178306 C>T), RS1000515455 (1:54182674 C>G), RS1000580440 (1:54183950 G>A), RS1000735266 (1:54177099 C>T), RS1000766528 (1:54177293 G>A,C), RS1000878030 (1:54200997 T>C), RS1000901342 (1:54195181 A>G), RS1001012063 (1:54182324 G>A), RS1001057233 (1:54169979 C>A), RS1001069829 (1:54188563 G>A,C), RS1001085405 (1:54169669 A>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90006993_3	Gut microbiota relative abundance (unclassified genus belonging to the order Clostridiales)	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
beta-lapachone	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	increases abundance, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Manganese	increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Rifampin	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.