CYB561D1

Summary

CYB561D1 (cytochrome b561 family member D1, HGNC:26804) is a protein-coding gene on chromosome 1p13.3, encoding Probable transmembrane reductase CYB561D1 (Q8N8Q1). Probable transmembrane reductase that may use ascorbate as an electron donor and transfer electrons across membranes to reduce monodehydro-L-ascorbate radical and iron cations Fe(3+) in another cellular compartment.

Predicted to enable metal ion binding activity; transmembrane ascorbate ferrireductase activity; and transmembrane monodehydroascorbate reductase activity. Predicted to be involved in transmembrane transport. Predicted to be located in membrane.

Source: NCBI Gene 284613 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 53 total
• MANE Select transcript: NM_182580

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26804
Approved symbol	CYB561D1
Name	cytochrome b561 family member D1
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ39035, FLJ44753
Ensembl gene	ENSG00000174151
Ensembl biotype	protein_coding
Entrez	284613

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000310611, ENST00000369868, ENST00000393709, ENST00000420578, ENST00000430195, ENST00000496961, ENST00000527072, ENST00000528785, ENST00000533024, ENST00000954036

RefSeq mRNA: 5 — MANE Select: NM_182580 NM_001134400, NM_001134402, NM_001134403, NM_001134404, NM_182580

CCDS: CCDS44188, CCDS44189, CCDS44190, CCDS44191, CCDS800

Canonical transcript exons

ENST00000420578 — 3 exons

Exon	Start	End
ENSE00001689540	109495756	109500435
ENSE00003602021	109495143	109495180
ENSE00003900405	109494094	109494287

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 92.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.7866 / max 54.2742, expressed in 1736 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4418	4.1195	1659
4419	0.9304	539
4417	0.7366	458

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	92.77	silver quality
pancreatic ductal cell	CL:0002079	91.84	silver quality
ileal mucosa	UBERON:0000331	91.19	gold quality
epithelial cell of pancreas	CL:0000083	88.66	gold quality
parotid gland	UBERON:0001831	87.56	silver quality
granulocyte	CL:0000094	87.38	gold quality
endothelial cell	CL:0000115	85.63	silver quality
upper leg skin	UBERON:0004262	84.73	gold quality
islet of Langerhans	UBERON:0000006	84.72	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	84.31	gold quality
blood	UBERON:0000178	83.55	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.43	gold quality
cerebellar hemisphere	UBERON:0002245	82.19	gold quality
cerebellar cortex	UBERON:0002129	82.10	gold quality
cerebellum	UBERON:0002037	81.89	gold quality
pancreas	UBERON:0001264	81.76	gold quality
nasal cavity epithelium	UBERON:0005384	81.28	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.16	gold quality
mammalian vulva	UBERON:0000997	80.80	silver quality
deltoid	UBERON:0001476	80.79	silver quality
body of pancreas	UBERON:0001150	80.65	gold quality
stromal cell of endometrium	CL:0002255	80.11	gold quality
tibialis anterior	UBERON:0001385	79.92	silver quality
leukocyte	CL:0000738	79.87	gold quality
lymph node	UBERON:0000029	79.56	gold quality
monocyte	CL:0000576	79.34	gold quality
middle temporal gyrus	UBERON:0002771	79.28	silver quality
decidua	UBERON:0002450	79.25	gold quality
right adrenal gland	UBERON:0001233	78.90	gold quality
prefrontal cortex	UBERON:0000451	78.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

129 targeting CYB561D1, 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-4283	100.00	66.42	2097
HSA-MIR-4692	100.00	67.32	2066
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-1184	99.99	68.19	1458
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6505-5P	99.73	69.25	1595

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cyb561d1	ENSDARG00000055295
mus_musculus	Cyb561d1	ENSMUSG00000048796
rattus_norvegicus	Cyb561d1	ENSRNOG00000052232
drosophila_melanogaster	CG10165	FBGN0032801
drosophila_melanogaster	CG13078	FBGN0032809
drosophila_melanogaster	CG13077	FBGN0032810

Paralogs (1): CYB561D2 (ENSG00000114395)

Protein

Protein identifiers

Probable transmembrane reductase CYB561D1 — Q8N8Q1 (reviewed: Q8N8Q1)

Alternative names: Cytochrome b561 domain-containing protein 1

All UniProt accessions (5): Q8N8Q1, E9PIJ2, E9PIK3, E9PM70, E9PQU0

UniProt curated annotations — full annotation on UniProt →

Function. Probable transmembrane reductase that may use ascorbate as an electron donor and transfer electrons across membranes to reduce monodehydro-L-ascorbate radical and iron cations Fe(3+) in another cellular compartment.

Subcellular location. Membrane.

Cofactor. Binds 2 heme b groups non-covalently.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8N8Q1-1	1	yes
Q8N8Q1-2	2
Q8N8Q1-3	3
Q8N8Q1-4	4
Q8N8Q1-5	5

RefSeq proteins (5): NP_001127872, NP_001127874, NP_001127875, NP_001127876, NP_872386* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006593	Cyt_b561/ferric_Rdtase_TM	Domain
IPR045150

Pfam: PF03188

Catalyzed reactions (Rhea), 2 shown:

• Fe(3+)(out) + L-ascorbate(in) = monodehydro-L-ascorbate radical(in) + Fe(2+)(out) + H(+) (RHEA:30403)
• monodehydro-L-ascorbate radical(out) + L-ascorbate(in) = monodehydro-L-ascorbate radical(in) + L-ascorbate(out) (RHEA:66524)

UniProt features (24 total): topological domain 7, transmembrane region 6, splice variant 5, binding site 4, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N8Q1-F1	88.31	0.68

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 (4): 55 (axial binding residue); 93 (axial binding residue); 127 (axial binding residue); 166 (axial binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 100 (showing top): RNGTGGGC_UNKNOWN, FOXD3_01, AGGCACT_MIR5153P, ZIC1_01, TATA_C, CCCNNGGGAR_OLF1_01, AP2_Q6_01, GOBP_TRANSMEMBRANE_TRANSPORT, OSMAN_BLADDER_CANCER_DN, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_METAL_IONS, GOMF_ACTIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, MMEF2_Q6, GOMF_TRANSPORTER_ACTIVITY

GO Biological Process (1): transmembrane transport (GO:0055085)

GO Molecular Function (4): metal ion binding (GO:0046872), transmembrane ascorbate ferrireductase activity (GO:0140571), transmembrane monodehydroascorbate reductase activity (GO:0140575), protein binding (GO:0005515)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	1
cellular process	1
cation binding	1
oxidoreduction-driven active transmembrane transporter activity	1
oxidoreductase activity, acting on metal ions	1
oxidoreductase activity	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

528 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYB561D1	GTF2A2	P52657	500
CYB561D1	SNX22	Q96L94	496
CYB561D1	BCCIP	Q9P287	455
CYB561D1	POLR3K	Q9Y2Y1	450
CYB561D1	ZNF701	Q9NV72	411
CYB561D1	SUOX	P51687	403
CYB561D1	EFNA4	P52798	396
CYB561D1	ASPDH	A6ND91	388
CYB561D1	CCDC9	Q9Y3X0	369
CYB561D1	KCNK6	Q9Y257	364
CYB561D1	TAS2R30	P59541	348
CYB561D1	CISD3	P0C7P0	338
CYB561D1	OR8U1	Q8NH10	336
CYB561D1	HRCT1	Q6UXD1	326
CYB561D1	FUT9	Q9Y231	324
CYB561D1	NBPF12	Q5TAG4	324

IntAct

13 interactions, top by confidence:

A	B	Type	Score
TMED8	CYB561D1	psi-mi:“MI:0915”(physical association)	0.560
GAD2	CYB561D1	psi-mi:“MI:0915”(physical association)	0.560
AQP6	CYB561D1	psi-mi:“MI:0915”(physical association)	0.560
CFTR	CYB561D1	psi-mi:“MI:0915”(physical association)	0.370
GAD2	CYB561D1	psi-mi:“MI:0915”(physical association)	0.000
TMED8	CYB561D1	psi-mi:“MI:0915”(physical association)	0.000
CYB561D1	AQP6	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): CYB561D1 (Two-hybrid), CYB561D1 (Two-hybrid), CYB561D1 (Two-hybrid), CYB561D1 (Affinity Capture-RNA), CYB561D1 (PCA)

ESM2 similar proteins: A2AE42, A3A9H6, A5D7C9, A5D9A7, A6NM10, B3SHH9, B5DFH9, B9EJG8, F1NZP5, O14569, P10897, P49447, P82352, Q08DE1, Q14714, Q148G2, Q3ZCD2, Q5E965, Q5ND56, Q5RCZ2, Q5U2W7, Q5ZJX0, Q60720, Q62147, Q641Y1, Q6GPL4, Q6P0C6, Q6P1H1, Q71RH2, Q7TNV1, Q80ZE4, Q86TG1, Q8BMD6, Q8C8S3, Q8IXF9, Q8N8Q1, Q8NBI2, Q8TBR7, Q8VHW3, Q8VHW7

Diamond homologs: A2AE42, O14569, Q5E965, Q641Y1, Q8N8Q1, Q9WUE3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

518 predictions. Top by Δscore:

Variant	Effect	Δscore
1:109494288:G:GG	donor_gain	1.0000
1:109495754:A:AG	acceptor_gain	0.9900
1:109495755:G:GG	acceptor_gain	0.9900
1:109494282:G:GT	donor_gain	0.9800
1:109494285:CCAG:C	donor_loss	0.9800
1:109494286:CAGT:C	donor_loss	0.9800
1:109494287:AG:A	donor_loss	0.9800
1:109494289:T:A	donor_loss	0.9800
1:109495755:GTTCT:G	acceptor_gain	0.9800
1:109494286:CA:C	donor_gain	0.9700
1:109494290:G:GC	donor_loss	0.9700
1:109494291:AGTG:A	donor_loss	0.9700
1:109494284:ACCA:A	donor_gain	0.9600
1:109494292:G:C	donor_loss	0.9600
1:109494237:T:TA	donor_gain	0.9500
1:109494238:A:AA	donor_gain	0.9500
1:109494285:CCA:C	donor_gain	0.9500
1:109495755:GTTC:G	acceptor_gain	0.9500
1:109495755:GTT:G	acceptor_gain	0.9300
1:109494283:A:T	donor_gain	0.9200
1:109495819:T:TA	acceptor_gain	0.9200
1:109495750:TCACA:T	acceptor_loss	0.9100
1:109495752:ACAG:A	acceptor_loss	0.9100
1:109495754:AG:A	acceptor_loss	0.9100
1:109496860:G:GT	donor_gain	0.8900
1:109494150:TGGAG:T	donor_loss	0.8600
1:109494153:AGGTA:A	donor_loss	0.8600
1:109494154:GG:G	donor_loss	0.8600
1:109494155:G:GC	donor_loss	0.8600
1:109494156:T:G	donor_loss	0.8600

AlphaMissense

1442 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:109495148:T:C	F52L	0.989
1:109495150:C:A	F52L	0.989
1:109495150:C:G	F52L	0.989
1:109496137:T:C	F190L	0.989
1:109496139:C:A	F190L	0.989
1:109496139:C:G	F190L	0.989
1:109495154:T:A	W54R	0.982
1:109495154:T:C	W54R	0.982
1:109495157:C:G	H55D	0.979
1:109496065:C:G	H166D	0.978
1:109495756:T:C	F63L	0.977
1:109495758:C:A	F63L	0.977
1:109495758:C:G	F63L	0.977
1:109496138:T:C	F190S	0.972
1:109495888:G:C	G107R	0.971
1:109496078:G:A	G170E	0.969
1:109495889:G:A	G107D	0.965
1:109495846:C:G	H93D	0.963
1:109495951:A:C	S128R	0.963
1:109495953:C:A	S128R	0.963
1:109495953:C:G	S128R	0.963
1:109494245:G:C	G36R	0.962
1:109495149:T:G	F52C	0.962
1:109496119:G:C	G184R	0.961
1:109496173:T:C	C202R	0.959
1:109495158:A:G	H55R	0.958
1:109495159:C:A	H55Q	0.958
1:109495159:C:G	H55Q	0.958
1:109496003:G:A	G145E	0.958
1:109496067:T:A	H166Q	0.957

dbSNP variants (sampled 300 via entrez): RS1000348149 (1:109497244 T>G), RS1000721964 (1:109492488 A>G,T), RS1000753328 (1:109492151 T>C), RS1000924584 (1:109497953 G>A,T), RS1000950288 (1:109498480 C>A), RS1000987062 (1:109492364 G>C), RS1001386302 (1:109498303 G>T), RS1001446779 (1:109498405 G>A,T), RS1001655845 (1:109494857 C>A,G), RS1001724465 (1:109493968 G>A,C,T), RS1001755570 (1:109493672 G>C), RS1001984381 (1:109499578 C>T), RS1002676971 (1:109499449 T>C), RS1002756649 (1:109494923 G>A,C), RS1003310284 (1:109496034 G>C,T)

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

7 associations (top):

Study	Trait	p-value
GCST000578_1	Major depressive disorder	6.000000e-06
GCST000649_1	Chronic kidney disease	1.000000e-07
GCST001762_843	Obesity-related traits	9.000000e-06
GCST004077_4	Cognitive function	8.000000e-07
GCST006269_1045	General cognitive ability	2.000000e-08
GCST008595_12	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	3.000000e-08
GCST008803_1	Smoking behaviour (cigarette pack-years)	3.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004574	total cholesterol measurement
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0009115	tobacco smoke exposure 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
Cisplatin	affects expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
beta-lapachone	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	increases abundance, affects cotreatment, decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Calcitriol	increases expression, affects cotreatment	1
Catechin	affects cotreatment, decreases expression	1
Diuron	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Plant Oils	increases expression	1
Smoke	decreases expression	1
Testosterone	affects cotreatment, increases expression	1
Urethane	increases expression	1
Lactic Acid	decreases expression	1
Volatile Organic Compounds	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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