RSAD1

Summary

RSAD1 (radical S-adenosyl methionine domain containing 1, HGNC:25634) is a protein-coding gene on chromosome 17q21.33, encoding Radical S-adenosyl methionine domain-containing protein 1, mitochondrial (Q9HA92). May be a heme chaperone, appears to bind heme. It is a selective cancer dependency (DepMap: 17.3% of cell lines).

Enables heme binding activity. Predicted to be involved in porphyrin-containing compound biosynthetic process. Located in mitochondrion.

Source: NCBI Gene 55316 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 83 total
• Cancer dependency (DepMap): dependent in 17.3% of screened cell lines
• MANE Select transcript: NM_018346

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25634
Approved symbol	RSAD1
Name	radical S-adenosyl methionine domain containing 1
Location	17q21.33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11164, HemW
Ensembl gene	ENSG00000136444
Ensembl biotype	protein_coding
OMIM	620590
Entrez	55316

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 9 protein_coding, 3 retained_intron, 3 nonsense_mediated_decay

ENST00000258955, ENST00000443328, ENST00000504284, ENST00000506211, ENST00000509398, ENST00000510554, ENST00000513650, ENST00000515221, ENST00000859048, ENST00000859049, ENST00000859050, ENST00000859051, ENST00000859052, ENST00000926999, ENST00000943159

RefSeq mRNA: 1 — MANE Select: NM_018346 NM_018346

CCDS: CCDS11569

Canonical transcript exons

ENST00000258955 — 9 exons

Exon	Start	End
ENSE00000737052	50479880	50480084
ENSE00001018465	50484744	50485974
ENSE00003479450	50482091	50482456
ENSE00003510924	50483340	50483487
ENSE00003520720	50484442	50484545
ENSE00003529405	50482643	50482706
ENSE00003557993	50479629	50479762
ENSE00003570893	50478860	50479019
ENSE00003659243	50483706	50483760

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 97.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.0605 / max 135.4164, expressed in 1789 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161667	11.0236	1767
161666	3.6861	1568
161665	1.3508	870

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	97.33	gold quality
cerebellar hemisphere	UBERON:0002245	97.23	gold quality
cerebellar cortex	UBERON:0002129	97.11	gold quality
body of pancreas	UBERON:0001150	96.15	gold quality
metanephros cortex	UBERON:0010533	95.94	gold quality
cerebellum	UBERON:0002037	95.91	gold quality
endocervix	UBERON:0000458	95.72	gold quality
apex of heart	UBERON:0002098	95.50	gold quality
right adrenal gland	UBERON:0001233	94.89	gold quality
gastrocnemius	UBERON:0001388	94.86	gold quality
left adrenal gland	UBERON:0001234	94.77	gold quality
right adrenal gland cortex	UBERON:0035827	94.77	gold quality
right lobe of thyroid gland	UBERON:0001119	94.71	gold quality
left adrenal gland cortex	UBERON:0035825	94.70	gold quality
body of stomach	UBERON:0001161	94.41	gold quality
right ovary	UBERON:0002118	94.37	gold quality
muscle of leg	UBERON:0001383	94.36	gold quality
left lobe of thyroid gland	UBERON:0001120	94.35	gold quality
adrenal cortex	UBERON:0001235	94.33	gold quality
left ovary	UBERON:0002119	94.13	gold quality
right frontal lobe	UBERON:0002810	94.01	gold quality
body of uterus	UBERON:0009853	93.96	gold quality
thyroid gland	UBERON:0002046	93.62	gold quality
right lobe of liver	UBERON:0001114	93.56	gold quality
ectocervix	UBERON:0012249	93.55	gold quality
adrenal gland	UBERON:0002369	93.50	gold quality
heart left ventricle	UBERON:0002084	93.27	gold quality
nucleus accumbens	UBERON:0001882	93.26	gold quality
putamen	UBERON:0001874	93.18	gold quality
right uterine tube	UBERON:0001302	92.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting RSAD1, 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-6748-5P	100.00	65.81	1057
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-6794-3P	98.76	66.99	894
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-3145-5P	98.57	67.83	900
HSA-MIR-6824-3P	98.44	67.62	1154

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 17.3% of screened cell lines.

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rsad1	ENSDARG00000077698
mus_musculus	Rsad1	ENSMUSG00000039096
rattus_norvegicus	Rsad1	ENSRNOG00000065974

Protein

Protein identifiers

Radical S-adenosyl methionine domain-containing protein 1, mitochondrial — Q9HA92 (reviewed: Q9HA92)

Alternative names: Putative heme chaperone

All UniProt accessions (4): Q9HA92, H0Y934, H0Y9X4, K7EKD3

UniProt curated annotations — full annotation on UniProt →

Function. May be a heme chaperone, appears to bind heme. Homologous bacterial proteins do not have oxygen-independent coproporphyrinogen-III oxidase activity. Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.

Subcellular location. Mitochondrion.

Miscellaneous. Might carry two S-adenosyl-L-methionine binding sites with only one binding to the iron-sulfur cluster.

Similarity. Belongs to the anaerobic coproporphyrinogen-III oxidase family. HemW subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9HA92-1	1	yes
Q9HA92-2	2

RefSeq proteins (1): NP_060816* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004559	HemW-like	Family
IPR006638	Elp3/MiaA/NifB-like_rSAM	Domain
IPR007197	rSAM	Domain
IPR010723	HemN_C	Domain
IPR013785	Aldolase_TIM	Homologous_superfamily
IPR034505	Coproporphyrinogen-III_oxidase	Family
IPR058240	rSAM_sf	Homologous_superfamily

Pfam: PF04055, PF06969

UniProt features (22 total): binding site 10, splice variant 3, sequence variant 3, sequence conflict 3, transit peptide 1, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HA92-F1	91.00	0.85

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 (10): 158; 170; 195; 43; 49; 53; 56; 98; 99–100; 131

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (1): porphyrin-containing compound biosynthetic process (GO:0006779)

GO Molecular Function (6): coproporphyrinogen oxidase activity (GO:0004109), heme binding (GO:0020037), metal ion binding (GO:0046872), 4 iron, 4 sulfur cluster binding (GO:0051539), catalytic activity (GO:0003824), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (2): cytoplasm (GO:0005737), mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
porphyrin-containing compound metabolic process	1
tetrapyrrole biosynthetic process	1
oxidoreductase activity, acting on the CH-CH group of donors, oxygen as acceptor	1
tetrapyrrole binding	1
cation binding	1
iron-sulfur cluster binding	1
molecular_function	1
metal cluster binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

3019 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RSAD1	TYW1	Q9NV66	505
RSAD1	MOCS1	Q9NZB8	490
RSAD1	PIGZ	Q86VD9	477
RSAD1	CDK5RAP1	Q96SZ6	475
RSAD1	DPM3	Q9P2X0	474
RSAD1	DPM2	O94777	462
RSAD1	ELP3	Q9H9T3	450
RSAD1	TMEM161A	Q9NX61	449
RSAD1	DPM1	O60762	448
RSAD1	RSAD2	Q8WXG1	444
RSAD1	METTL25B	Q96FB5	444
RSAD1	CZIB	Q9NWV4	435
RSAD1	GARRE1	O15063	433
RSAD1	BOLA1	Q9Y3E2	422
RSAD1	OR5H14	A6NHG9	418
RSAD1	THNSL1	Q8IYQ7	418

IntAct

63 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NDUFS6	NDUFS8	psi-mi:“MI:0914”(association)	0.640
BPNT1	GTPBP10	psi-mi:“MI:0914”(association)	0.530
KLHDC2	PFDN1	psi-mi:“MI:0914”(association)	0.530
PNLIP	LAMC1	psi-mi:“MI:0914”(association)	0.530
WDR53	BLVRA	psi-mi:“MI:0914”(association)	0.530
ARHGEF26	CPS1	psi-mi:“MI:0914”(association)	0.530
WDR53	NACAD	psi-mi:“MI:0914”(association)	0.350
TRMT1	HDAC3	psi-mi:“MI:0914”(association)	0.350
LIG3	NDUFS6	psi-mi:“MI:0914”(association)	0.350
SDHB	CLPX	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
MGARP	BTAF1	psi-mi:“MI:0914”(association)	0.350
ZNF460	ZNF320	psi-mi:“MI:0914”(association)	0.350
UQCRFS1	VWA8	psi-mi:“MI:0914”(association)	0.350
FBLN2	ZNF316	psi-mi:“MI:0914”(association)	0.350
PTH2R	METTL15	psi-mi:“MI:0914”(association)	0.350
RTCA	NDUFA4	psi-mi:“MI:0914”(association)	0.350
TRAV20	MAP2K7	psi-mi:“MI:0914”(association)	0.350
TRMU	IFT56	psi-mi:“MI:0914”(association)	0.350
TRIM43	VWA8	psi-mi:“MI:0914”(association)	0.350
QRSL1	VWA8	psi-mi:“MI:0914”(association)	0.350
SHC2	VWA8	psi-mi:“MI:0914”(association)	0.350
YARS2	VWA8	psi-mi:“MI:0914”(association)	0.350
MRPS24	VWA8	psi-mi:“MI:0914”(association)	0.350
AMACR	VWA8	psi-mi:“MI:0914”(association)	0.350
ACSM5	VWA8	psi-mi:“MI:0914”(association)	0.350
AK4	VWA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (59): RSAD1 (Affinity Capture-MS), RSAD1 (Affinity Capture-MS), RSAD1 (Affinity Capture-MS), RSAD1 (Affinity Capture-MS), RSAD1 (Affinity Capture-MS), RSAD1 (Affinity Capture-MS), RSAD1 (Affinity Capture-MS), RSAD1 (Affinity Capture-MS), RSAD1 (Affinity Capture-MS), RSAD1 (Affinity Capture-MS), RSAD1 (Affinity Capture-MS), RSAD1 (Affinity Capture-MS), RSAD1 (Affinity Capture-MS), RSAD1 (Affinity Capture-MS), RSAD1 (Affinity Capture-MS)

ESM2 similar proteins: A4FV98, A5D7B1, A5PK51, A6QLN9, A8MUP2, D3ZVU9, O15527, O35595, O75078, O95848, P57775, Q05B60, Q06643, Q14728, Q14CX5, Q1LZB9, Q27HK4, Q2T9T5, Q2TBS1, Q3UGX3, Q4R3I0, Q4V892, Q58CT4, Q5E9H2, Q5RCI5, Q5SUV1, Q5TM22, Q642A6, Q6IA17, Q6PCB0, Q6XQN6, Q862Z7, Q8N8L6, Q8R2R5, Q8R2Z5, Q8R366, Q8WUG5, Q95JH0, Q95JH2, Q969P0

Diamond homologs: A4IGH2, A5D7B1, P43899, P52062, P54304, P73245, P95506, P9WP72, P9WP73, Q54VE8, Q5SUV1, Q8K928, Q9HA92, O34162, P57615, P77915, O67886, P0A1E1, P0A1E2, P32131, P74132, Q89A47, Q9CGF7, Q51676, O31381, P33770, P55477, P95651, Q796V8, O25376, O31067, O59545, P51008, Q9ZLH0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1656 predictions. Top by Δscore:

Variant	Effect	Δscore
17:50479020:G:GG	donor_gain	1.0000
17:50479627:A:AG	acceptor_gain	1.0000
17:50479627:AGT:A	acceptor_gain	1.0000
17:50479628:G:GG	acceptor_gain	1.0000
17:50479628:GT:G	acceptor_gain	1.0000
17:50479628:GTG:G	acceptor_gain	1.0000
17:50479759:AACGG:A	donor_loss	1.0000
17:50479761:CGG:C	donor_loss	1.0000
17:50479762:GGT:G	donor_loss	1.0000
17:50479763:G:T	donor_loss	1.0000
17:50479989:G:GT	donor_gain	1.0000
17:50482089:A:AG	acceptor_gain	1.0000
17:50482090:G:GG	acceptor_gain	1.0000
17:50482452:GGAAT:G	donor_gain	1.0000
17:50482453:GAAT:G	donor_gain	1.0000
17:50482453:GAATG:G	donor_gain	1.0000
17:50482454:A:T	donor_gain	1.0000
17:50482457:G:GG	donor_gain	1.0000
17:50482457:GTAA:G	donor_loss	1.0000
17:50482458:T:G	donor_loss	1.0000
17:50483485:GCT:G	donor_gain	1.0000
17:50478967:G:GT	donor_gain	0.9900
17:50479015:TACAC:T	donor_gain	0.9900
17:50479018:AC:A	donor_gain	0.9900
17:50479018:ACGT:A	donor_loss	0.9900
17:50479020:G:GC	donor_loss	0.9900
17:50479021:TGA:T	donor_loss	0.9900
17:50479022:GAGTA:G	donor_loss	0.9900
17:50479023:AGT:A	donor_loss	0.9900
17:50479620:T:A	acceptor_gain	0.9900

AlphaMissense

2800 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:50479665:T:C	F58L	0.996
17:50479667:C:A	F58L	0.996
17:50479667:C:G	F58L	0.996
17:50480065:G:T	R152M	0.994
17:50482701:G:A	G300E	0.994
17:50479893:T:C	F95L	0.993
17:50479895:C:A	F95L	0.993
17:50479895:C:G	F95L	0.993
17:50479914:A:C	S102R	0.993
17:50479916:T:A	S102R	0.993
17:50479916:T:G	S102R	0.993
17:50483422:G:C	W329C	0.992
17:50483422:G:T	W329C	0.992
17:50479660:G:A	C56Y	0.991
17:50479629:T:A	W46R	0.990
17:50479629:T:C	W46R	0.990
17:50479017:C:G	H45D	0.989
17:50480003:G:C	E131D	0.989
17:50480003:G:T	E131D	0.989
17:50482445:T:C	F277L	0.989
17:50482447:T:A	F277L	0.989
17:50482447:T:G	F277L	0.989
17:50483420:T:A	W329R	0.989
17:50483420:T:C	W329R	0.989
17:50482444:C:A	N276K	0.988
17:50482444:C:G	N276K	0.988
17:50482652:A:C	S284R	0.988
17:50482654:T:A	S284R	0.988
17:50482654:T:G	S284R	0.988
17:50479639:G:A	C49Y	0.987

dbSNP variants (sampled 300 via entrez): RS1000136382 (17:50479538 AGGGGTG>A,AGGGGTGGGGGTG), RS1000176049 (17:50481556 T>C), RS1000580099 (17:50479839 A>C), RS1000696835 (17:50481310 C>G,T), RS1001075304 (17:50485672 C>G,T), RS1001320411 (17:50484205 G>T), RS1001556946 (17:50480546 G>A), RS1001598676 (17:50479265 T>C), RS1001777657 (17:50480847 C>T), RS1001964726 (17:50485133 C>A,T), RS1002324793 (17:50477757 G>T), RS1003063199 (17:50478105 C>A,T), RS1003792216 (17:50478333 G>A), RS1004390154 (17:50479819 G>A,C,T), RS1004712025 (17:50484742 A>G)

Disease associations

OMIM: gene MIM:620590 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

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
Acetaminophen	decreases expression, increases expression	2
Cisplatin	affects cotreatment, increases expression, decreases expression	2
Valproic Acid	increases expression, affects expression	2
pirinixic acid	affects binding, increases activity, increases expression	1
trichostatin A	increases expression	1
methylparaben	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	increases expression	1
Methotrexate	increases expression	1
Methyl Methanesulfonate	decreases expression	1
Quercetin	decreases expression	1
Rotenone	increases expression	1
Selenium	increases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Vitamin E	increases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1
Vitamin K 3	affects expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TJ80	HAP1 RSAD1 (-) 1	Cancer cell line	Male
CVCL_XS32	HAP1 RSAD1 (-) 2	Cancer cell line	Male
CVCL_XS33	HAP1 RSAD1 (-) 3	Cancer cell line	Male
CVCL_XS34	HAP1 RSAD1 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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