SRRD

Summary

SRRD (SRR1 domain containing, HGNC:33910) is a protein-coding gene on chromosome 22q12.1, encoding SRR1-like protein (Q9UH36). Plays a role in the regulation of heme biosynthesis and in the regulation of the expression of core clock genes. It is a selective cancer dependency (DepMap: 12.3% of cell lines).

Predicted to be involved in regulation of circadian rhythm and regulation of heme biosynthetic process. Predicted to be active in cytoplasm and nucleus.

Source: NCBI Gene 402055 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 74 total
• Cancer dependency (DepMap): dependent in 12.3% of screened cell lines
• MANE Select transcript: NM_001013694

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33910
Approved symbol	SRRD
Name	SRR1 domain containing
Location	22q12.1
Locus type	gene with protein product
Status	Approved
Aliases	HC/HCC, SRR1L
Ensembl gene	ENSG00000100104
Ensembl biotype	protein_coding
OMIM	602254
Entrez	402055

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 retained_intron

ENST00000215917, ENST00000471799, ENST00000477945, ENST00000885114, ENST00000885115, ENST00000942937, ENST00000942938

RefSeq mRNA: 1 — MANE Select: NM_001013694 NM_001013694

CCDS: CCDS42995

Canonical transcript exons

ENST00000215917 — 7 exons

Exon	Start	End
ENSE00000651891	26486023	26486063
ENSE00000651892	26488029	26488288
ENSE00001316858	26491463	26494658
ENSE00001319017	26483877	26484099
ENSE00003529773	26488390	26488488
ENSE00003566791	26490044	26490198
ENSE00003665610	26491025	26491070

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 92.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.6857 / max 205.8640, expressed in 1813 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191506	25.4004	1812
191507	0.2853	102

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	92.03	gold quality
muscle of leg	UBERON:0001383	91.72	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.85	gold quality
muscle organ	UBERON:0001630	90.37	gold quality
islet of Langerhans	UBERON:0000006	88.63	gold quality
sperm	CL:0000019	87.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.80	gold quality
vastus lateralis	UBERON:0001379	87.80	gold quality
blood	UBERON:0000178	87.70	gold quality
quadriceps femoris	UBERON:0001377	87.42	gold quality
male germ cell	CL:0000015	87.22	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	87.07	gold quality
skeletal muscle tissue	UBERON:0001134	87.06	gold quality
diaphragm	UBERON:0001103	87.05	gold quality
cortical plate	UBERON:0005343	87.00	gold quality
colonic epithelium	UBERON:0000397	86.46	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.39	gold quality
bone marrow	UBERON:0002371	86.10	gold quality
pancreas	UBERON:0001264	86.00	gold quality
deltoid	UBERON:0001476	85.70	gold quality
body of pancreas	UBERON:0001150	85.65	gold quality
biceps brachii	UBERON:0001507	85.51	gold quality
right testis	UBERON:0004534	85.39	gold quality
muscle tissue	UBERON:0002385	85.32	gold quality
smooth muscle tissue	UBERON:0001135	85.15	gold quality
left testis	UBERON:0004533	85.12	gold quality
bone marrow cell	CL:0002092	85.10	gold quality
prefrontal cortex	UBERON:0000451	85.06	gold quality
testis	UBERON:0000473	84.86	gold quality
right lobe of thyroid gland	UBERON:0001119	84.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting SRRD, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-6721-5P	99.93	68.92	2981
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-4495	99.82	72.08	3080
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-1265	98.36	66.46	598
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-510-5P	97.66	65.82	916
HSA-MIR-6742-5P	96.32	64.01	869
HSA-MIR-6834-5P	96.25	64.88	823

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 12.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• CRISPR screen for protein inclusion formation uncovers a role for SRRD in the regulation of intermediate filament dynamics and aggresome assembly. (PMID:38315730)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	srrd	ENSDARG00000059028
mus_musculus	Srrd	ENSMUSG00000029346
rattus_norvegicus	Srrd	ENSRNOG00000000662
drosophila_melanogaster	CG7988	FBGN0038582

Protein

Protein identifiers

SRR1-like protein — Q9UH36 (reviewed: Q9UH36)

Alternative names: SRR1 domain-containing protein

All UniProt accessions (1): Q9UH36

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the regulation of heme biosynthesis and in the regulation of the expression of core clock genes.

Subcellular location. Cytoplasm.

Induction. Up-regulated by hemin and 5-aminolevulinic acid.

Similarity. Belongs to the SRR1 family.

RefSeq proteins (1): NP_001013716* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012942	SRR1-like	Domain
IPR040044	SRR1L	Family

Pfam: PF07985

UniProt features (12 total): repeat 3, compositionally biased region 3, sequence variant 2, region of interest 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UH36-F1	79.45	0.65

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 89 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_TETRAPYRROLE_BIOSYNTHETIC_PROCESS, CHANDRAN_METASTASIS_DN, GOBP_PORPHYRIN_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_REGULATION_OF_CIRCADIAN_RHYTHM, AMIT_EGF_RESPONSE_480_MCF10A, GOBP_TETRAPYRROLE_METABOLIC_PROCESS, GOBP_PIGMENT_METABOLIC_PROCESS, WANG_CISPLATIN_RESPONSE_AND_XPC_DN, GOBP_PIGMENT_BIOSYNTHETIC_PROCESS, ACEVEDO_LIVER_CANCER_UP, GOBP_RHYTHMIC_PROCESS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_DN, BRUINS_UVC_RESPONSE_LATE, DIDO1_TARGET_GENES

GO Biological Process (4): heme biosynthetic process (GO:0006783), regulation of circadian rhythm (GO:0042752), rhythmic process (GO:0048511), regulation of heme biosynthetic process (GO:0070453)

GO Molecular Function (0):

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
porphyrin-containing compound biosynthetic process	1
heme metabolic process	1
pigment biosynthetic process	1
circadian rhythm	1
regulation of biological process	1
biological_process	1
heme biosynthetic process	1
regulation of tetrapyrrole biosynthetic process	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

360 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRRD	ASPHD2	Q6ICH7	636
SRRD	TPST2	O60704	511
SRRD	SEZ6L	Q9BYH1	470
SRRD	ANKRD42	Q8N9B4	415
SRRD	HNRNPLL	Q8WVV9	404
SRRD	MYO18B	Q8IUG5	402
SRRD	CRYBA4	P53673	376
SRRD	BSN	Q9UPA5	356
SRRD	HPS4	Q9NQG7	351
SRRD	FLAD1	Q8NFF5	348
SRRD	HPS6	Q86YV9	341
SRRD	ASPHD1	Q5U4P2	330
SRRD	RFK	Q969G6	314
SRRD	STT3B	Q8TCJ2	301
SRRD	KCTD15	Q96SI1	298

IntAct

2 interactions, top by confidence:

A	B	Type	Score
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): SRRD (Affinity Capture-RNA), SRRD (Affinity Capture-RNA), SRRD (Affinity Capture-MS), SRRD (Negative Genetic), SRRD (Positive Genetic), SRRD (Affinity Capture-RNA)

ESM2 similar proteins: A2AUU0, A3KMI0, E7F654, F1MAB7, P33279, P59114, Q08DH3, Q0P5B2, Q13686, Q28H30, Q3T131, Q3T9Z9, Q49AR2, Q4R8E0, Q5R5W9, Q5R6T6, Q5U2S3, Q5ZLL7, Q62240, Q63185, Q6DTM3, Q6NXH8, Q6NZP1, Q6P1Q9, Q6PAE6, Q6PD74, Q6ZUJ8, Q7SZF1, Q7TNN8, Q7Z3E5, Q8BGC1, Q8BMD7, Q8BMK1, Q8CHK4, Q8K3E5, Q8N6Q8, Q8TE76, Q8W5R2, Q92993, Q96IZ6

Diamond homologs: Q8GWZ6, Q8K2M3, Q9UH36, Q9VEB5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1313 predictions. Top by Δscore:

Variant	Effect	Δscore
22:26484095:GC:G	donor_gain	1.0000
22:26484100:G:GG	donor_gain	1.0000
22:26491541:T:A	acceptor_gain	1.0000
22:26492367:ACC:A	acceptor_loss	1.0000
22:26492368:CCTA:C	acceptor_loss	1.0000
22:26492369:CTAAG:C	acceptor_loss	1.0000
22:26494135:TTA:T	donor_loss	1.0000
22:26494136:TA:T	donor_loss	1.0000
22:26494136:TACCA:T	donor_gain	1.0000
22:26494137:A:AC	donor_gain	1.0000
22:26494137:A:C	donor_loss	1.0000
22:26494137:ACCAA:A	donor_gain	1.0000
22:26494138:C:CC	donor_gain	1.0000
22:26494138:CCA:C	donor_gain	1.0000
22:26494138:CCAA:C	donor_gain	1.0000
22:26494138:CCAAC:C	donor_gain	1.0000
22:26494300:AGCAC:A	acceptor_gain	1.0000
22:26494302:CAC:C	acceptor_gain	1.0000
22:26494303:ACCT:A	acceptor_loss	1.0000
22:26494305:C:CC	acceptor_gain	1.0000
22:26494306:T:C	acceptor_loss	1.0000
22:26484092:GAGGC:G	donor_gain	0.9900
22:26484095:GCTGA:G	donor_gain	0.9900
22:26484096:C:G	donor_gain	0.9900
22:26484098:GA:G	donor_gain	0.9900
22:26486656:GCA:G	donor_gain	0.9900
22:26486681:T:G	donor_gain	0.9900
22:26488253:C:G	donor_gain	0.9900
22:26488283:TGCC:T	donor_gain	0.9900
22:26488384:TTCTA:T	acceptor_loss	0.9900

AlphaMissense

2211 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:26490115:C:A	N227K	0.985
22:26490115:C:G	N227K	0.985
22:26490120:T:C	L229P	0.981
22:26488205:T:C	C143R	0.980
22:26490092:C:G	H220D	0.979
22:26490123:T:C	L230S	0.979
22:26490171:G:A	G246E	0.979
22:26490170:G:T	G246W	0.978
22:26490047:G:T	G205W	0.977
22:26488254:T:C	L159P	0.976
22:26488218:G:A	G147E	0.975
22:26490097:T:G	C221W	0.973
22:26490118:T:A	N228K	0.973
22:26490118:T:G	N228K	0.973
22:26490171:G:T	G246V	0.973
22:26490114:A:T	N227I	0.972
22:26491520:T:C	F290L	0.972
22:26491522:T:A	F290L	0.972
22:26491522:T:G	F290L	0.972
22:26488207:T:G	C143W	0.971
22:26488242:C:A	A155D	0.971
22:26488218:G:T	G147V	0.970
22:26488485:C:A	N202K	0.970
22:26488485:C:G	N202K	0.970
22:26490096:G:A	C221Y	0.970
22:26490134:T:A	W234R	0.968
22:26490134:T:C	W234R	0.968
22:26488199:T:C	C141R	0.967
22:26488451:T:C	L191P	0.967
22:26490094:T:A	H220Q	0.967

dbSNP variants (sampled 300 via entrez): RS1000110642 (22:26484302 G>C), RS1000157257 (22:26489163 GAA>G), RS1000179881 (22:26483517 G>A,T), RS1000903600 (22:26490721 G>A,C,T), RS1001051785 (22:26484207 A>G), RS1001748783 (22:26485669 T>A), RS1002030009 (22:26487187 C>G), RS1002158596 (22:26486172 G>A,T), RS1002458879 (22:26493045 A>G), RS1002485585 (22:26487475 T>C), RS1002755644 (22:26489894 A>C), RS1002878900 (22:26493611 C>T), RS1002929798 (22:26493881 G>C), RS1003050258 (22:26487416 G>A,C), RS1003074265 (22:26493337 A>G)

Disease associations

OMIM: gene MIM:602254 | 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

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Plant Extracts	increases expression, affects cotreatment	1
Tobacco Smoke Pollution	decreases expression	1
tert-Butylhydroperoxide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2KU	HAP1 SRRD (-) 1	Cancer cell line	Male
CVCL_E2KV	HAP1 SRRD (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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