CYB5D1

Summary

CYB5D1 (cytochrome b5 domain containing 1, HGNC:26516) is a protein-coding gene on chromosome 17p13.1, encoding Cytochrome b5 domain-containing protein 1 (Q6P9G0). Radial spoke stalk protein that binds heme under oxidizing conditions.

Predicted to enable metal ion binding activity. Predicted to be involved in cilium movement and regulation of cilium beat frequency. Predicted to be located in cell projection; cytoplasm; and cytoskeleton.

Source: NCBI Gene 124637 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 51 total
• MANE Select transcript: NM_144607

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26516
Approved symbol	CYB5D1
Name	cytochrome b5 domain containing 1
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32499
Ensembl gene	ENSG00000182224
Ensembl biotype	protein_coding
Entrez	124637

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000332439, ENST00000570446, ENST00000571846, ENST00000573940, ENST00000574196, ENST00000574357

RefSeq mRNA: 2 — MANE Select: NM_144607 NM_001330110, NM_144607

CCDS: CCDS11123, CCDS82061

Canonical transcript exons

ENST00000332439 — 4 exons

Exon	Start	End
ENSE00001372987	7859382	7862282
ENSE00002665400	7858003	7858294
ENSE00003363076	7858403	7858479
ENSE00003648250	7858606	7858824

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 94.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.6514 / max 43.0608, expressed in 1656 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159422	4.1096	1531
159421	1.5417	999

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	94.92	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.82	gold quality
fallopian tube	UBERON:0003889	87.79	gold quality
apex of heart	UBERON:0002098	86.96	gold quality
right lobe of thyroid gland	UBERON:0001119	86.84	gold quality
thyroid gland	UBERON:0002046	86.69	gold quality
pituitary gland	UBERON:0000007	86.66	gold quality
left lobe of thyroid gland	UBERON:0001120	86.60	gold quality
adenohypophysis	UBERON:0002196	86.55	gold quality
cortical plate	UBERON:0005343	85.70	gold quality
heart left ventricle	UBERON:0002084	85.41	gold quality
adult mammalian kidney	UBERON:0000082	85.15	gold quality
right adrenal gland	UBERON:0001233	84.98	gold quality
right adrenal gland cortex	UBERON:0035827	84.85	gold quality
calcaneal tendon	UBERON:0003701	84.64	gold quality
left adrenal gland	UBERON:0001234	84.54	gold quality
omental fat pad	UBERON:0010414	84.38	gold quality
metanephros cortex	UBERON:0010533	84.02	gold quality
left adrenal gland cortex	UBERON:0035825	83.95	gold quality
kidney	UBERON:0002113	83.79	gold quality
heart	UBERON:0000948	83.63	gold quality
adrenal gland	UBERON:0002369	83.53	gold quality
cortex of kidney	UBERON:0001225	83.34	gold quality
endometrium	UBERON:0001295	83.19	gold quality
body of pancreas	UBERON:0001150	83.17	gold quality
prostate gland	UBERON:0002367	82.90	gold quality
caudate nucleus	UBERON:0001873	82.75	gold quality
nucleus accumbens	UBERON:0001882	82.60	gold quality
body of uterus	UBERON:0009853	82.60	gold quality
endocervix	UBERON:0000458	82.59	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	399.90
E-ANND-3	no	1.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

113 targeting CYB5D1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cyb5d1	ENSDARG00000056007
mus_musculus	Cyb5d1	ENSMUSG00000044795
rattus_norvegicus	Cyb5d1	ENSRNOG00000066275
drosophila_melanogaster	CG15429	FBGN0031596

Protein

Protein identifiers

Cytochrome b5 domain-containing protein 1 — Q6P9G0 (reviewed: Q6P9G0)

All UniProt accessions (3): Q6P9G0, I3L321, I3NI34

UniProt curated annotations — full annotation on UniProt →

Function. Radial spoke stalk protein that binds heme under oxidizing conditions. Required for the coordinated beating of multiple cilia maybe by functioning in a redox signaling pathway.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium axoneme.

Similarity. Belongs to the cytochrome b5 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6P9G0-1	1	yes
Q6P9G0-2	2

RefSeq proteins (2): NP_001317039, NP_653208* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001199	Cyt_B5-like_heme/steroid-bd	Domain
IPR036400	Cyt_B5-like_heme/steroid_sf	Homologous_superfamily
IPR052320	Cytochrome_b5_domain	Family

Pfam: PF00173

UniProt features (7 total): binding site 2, splice variant 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8J07	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P9G0-F1	87.02	0.52

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): 52 (axial binding residue); 83 (axial binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 94 (showing top): RNGTGGGC_UNKNOWN, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, LFA1_Q6, SOX9_B1, GATA3_01, GOBP_CILIUM_MOVEMENT, TCF11_01, GOBP_REGULATION_OF_MICROTUBULE_BASED_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_REGULATION_OF_CILIUM_MOVEMENT, GRADE_COLON_AND_RECTAL_CANCER_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, TGGAAA_NFAT_Q4_01, GOCC_CYTOPLASMIC_REGION, GOCC_MOTILE_CILIUM

GO Biological Process (2): cilium movement (GO:0003341), regulation of cilium beat frequency (GO:0003356)

GO Molecular Function (1): metal ion binding (GO:0046872)

GO Cellular Component (4): axoneme (GO:0005930), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
microtubule-based movement	1
regulation of cilium movement	1
cation binding	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1711 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYB5D1	MRPS31	Q92665	489
CYB5D1	NAA38	Q9BRA0	475
CYB5D1	TEKT1	Q969V4	472
CYB5D1	CFAP58	Q5T655	457
CYB5D1	SUOX	P51687	447
CYB5D1	DRC11	Q86XH1	429
CYB5D1	MTG2	Q9H4K7	428
CYB5D1	ABRAXAS2	Q15018	425
CYB5D1	EDAR	Q9UNE0	422
CYB5D1	CYB5R4	Q7L1T6	408
CYB5D1	IPO5	O00410	401
CYB5D1	DNAJC24	Q6P3W2	401
CYB5D1	DNAJC3	Q13217	399
CYB5D1	ZNF841	Q6ZN19	399
CYB5D1	METTL25B	Q96FB5	395
CYB5D1	WASF2	Q9Y6W5	395

IntAct

2 interactions, top by confidence:

A	B	Type	Score
DCUN1D1	RGSL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): CYB5D1 (Affinity Capture-RNA), CYB5D1 (Proximity Label-MS), CYB5D1 (Proximity Label-MS), CYB5D1 (Affinity Capture-MS)

ESM2 similar proteins: O14349, O41515, P08509, P11035, P11605, P11832, P17569, P17570, P27783, P34426, P36859, P39864, P39865, P39867, P39868, P39870, P43101, P49050, P54233, P81128, P83509, P97393, Q08BZ4, Q09879, Q0IHR1, Q13017, Q14AI0, Q1DKI1, Q21407, Q2RBS4, Q51MW4, Q567I9, Q5E951, Q5NCY3, Q5PPR6, Q5QFG1, Q5R4Q5, Q67Z52, Q6GL75, Q6GMB0

Diamond homologs: A0A286R227, A9SIZ6, B7GCG7, B8MKR3, C8VJR5, I2CYZ4, O04354, O22704, O43169, O48845, O74212, O74875, O94391, O96099, P00167, P00168, P00169, P00170, P00171, P00172, P00173, P00174, P00175, P04166, P08509, P09437, P11035, P11605, P11832, P16081, P17569, P17571, P23312, P27783, P27967, P27968, P27969, P32953, P36841, P36842

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

415 predictions. Top by Δscore:

Variant	Effect	Δscore
17:7858291:AAGG:A	donor_gain	1.0000
17:7858292:AGG:A	donor_gain	1.0000
17:7858293:GG:G	donor_gain	1.0000
17:7858293:GGG:G	donor_gain	1.0000
17:7858294:GG:G	donor_gain	1.0000
17:7858295:G:GG	donor_gain	1.0000
17:7858296:T:A	donor_loss	1.0000
17:7858400:A:AG	acceptor_gain	1.0000
17:7858400:AAG:A	acceptor_gain	1.0000
17:7858400:AAGG:A	acceptor_gain	1.0000
17:7858401:A:G	acceptor_gain	1.0000
17:7858475:GAGAC:G	donor_gain	1.0000
17:7858477:GAC:G	donor_gain	1.0000
17:7858480:G:GG	donor_gain	1.0000
17:7858485:T:G	donor_gain	1.0000
17:7859441:T:G	acceptor_gain	1.0000
17:7858285:G:GT	donor_gain	0.9900
17:7858290:CAAGG:C	donor_gain	0.9900
17:7858397:TTCAA:T	acceptor_loss	0.9900
17:7858398:TCAA:T	acceptor_loss	0.9900
17:7858399:CAAGG:C	acceptor_loss	0.9900
17:7858401:AG:A	acceptor_gain	0.9900
17:7858402:G:GA	acceptor_loss	0.9900
17:7858402:G:GG	acceptor_gain	0.9900
17:7858402:GG:G	acceptor_gain	0.9900
17:7858476:AGAC:A	donor_gain	0.9900
17:7858477:GACG:G	donor_gain	0.9900
17:7858478:AC:A	donor_gain	0.9900
17:7858479:CG:C	donor_loss	0.9900
17:7858480:G:GA	donor_loss	0.9900

AlphaMissense

1483 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:7859457:T:A	W178R	0.991
17:7859457:T:C	W178R	0.991
17:7858726:T:A	W120R	0.988
17:7858726:T:C	W120R	0.988
17:7858729:T:A	W121R	0.985
17:7858729:T:C	W121R	0.985
17:7858459:T:C	F73L	0.984
17:7858461:T:A	F73L	0.984
17:7858461:T:G	F73L	0.984
17:7859586:T:C	F221L	0.984
17:7859588:C:A	F221L	0.984
17:7859588:C:G	F221L	0.984
17:7858794:C:A	N142K	0.982
17:7858794:C:G	N142K	0.982
17:7859443:C:A	A173D	0.979
17:7859419:G:C	R165P	0.978
17:7858456:T:A	W72R	0.976
17:7858456:T:C	W72R	0.976
17:7858450:A:C	S70R	0.975
17:7858452:C:A	S70R	0.975
17:7858452:C:G	S70R	0.975
17:7858237:T:A	W35R	0.971
17:7858237:T:C	W35R	0.971
17:7858460:T:C	F73S	0.971
17:7858728:G:C	W120C	0.970
17:7858728:G:T	W120C	0.970
17:7858439:G:A	G66D	0.969
17:7859451:T:C	Y176H	0.968
17:7859575:T:A	I217K	0.967
17:7858731:G:C	W121C	0.966

dbSNP variants (sampled 300 via entrez): RS1000378794 (17:7856253 C>G,T), RS1000749924 (17:7856110 G>A,C), RS1000828452 (17:7860120 T>C), RS1000940754 (17:7860588 G>A,T), RS1001352322 (17:7857096 T>C), RS1001585524 (17:7861200 G>C), RS1001850162 (17:7856143 G>T), RS1004682620 (17:7859694 C>T), RS1005187078 (17:7856715 G>A,T), RS1005627589 (17:7862140 G>A), RS1005646319 (17:7856405 A>G), RS1005902986 (17:7856496 C>T), RS1005940779 (17:7861102 G>C,T), RS1006517065 (17:7860415 C>T), RS1007040813 (17:7860755 G>A,C)

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

2 associations (top):

Study	Trait	p-value
GCST010703_158	Brain morphology (MOSTest)	3.000000e-09
GCST90002402_438	Platelet count	2.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression, increases methylation, affects expression	4
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression, increases expression	3
potassium chromate(VI)	increases expression, affects cotreatment	2
Estradiol	affects cotreatment, increases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
methylmercuric chloride	decreases expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
potassium perchlorate	decreases expression	1
sodium arsenite	increases abundance, increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
epigallocatechin gallate	affects cotreatment, increases expression	1
chromium hexavalent ion	increases expression	1
bisphenol S	decreases methylation	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Fulvestrant	increases methylation	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Cytarabine	decreases expression	1
Bucladesine	increases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Smoke	increases abundance, increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Vanadium	increases abundance, increases methylation	1
Medroxyprogesterone Acetate	affects cotreatment, increases expression	1
Metals, Heavy	increases abundance, increases methylation	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

Clinical trials (associated diseases)

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