SRL

Summary

SRL (sarcalumenin, HGNC:11295) is a protein-coding gene on chromosome 16p13.3, encoding Sarcalumenin (Q86TD4).

Predicted to enable GTP binding activity. Predicted to be involved in store-operated calcium entry. Predicted to act upstream of or within response to muscle activity involved in regulation of muscle adaptation. Predicted to be located in sarcoplasmic reticulum lumen and sarcoplasmic reticulum membrane.

Source: NCBI Gene 6345 — RefSeq curated summary.

At a glance

• GWAS associations: 48
• Clinical variants (ClinVar): 77 total — 1 pathogenic
• MANE Select transcript: NM_001098814

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11295
Approved symbol	SRL
Name	sarcalumenin
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	SAR
Ensembl gene	ENSG00000185739
Ensembl biotype	protein_coding
OMIM	604992
Entrez	6345

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 nonsense_mediated_decay

ENST00000399609, ENST00000537996, ENST00000572111, ENST00000855673, ENST00000967596, ENST00000967597, ENST00000967598, ENST00000967599, ENST00000967600, ENST00000967601, ENST00000967602, ENST00000967603

RefSeq mRNA: 3 — MANE Select: NM_001098814 NM_001098814, NM_001323667, NM_001323668

CCDS: CCDS42113, CCDS81943

Canonical transcript exons

ENST00000399609 — 6 exons

Exon	Start	End
ENSE00001417289	4242007	4242080
ENSE00003525245	4203166	4203261
ENSE00003534037	4204533	4204634
ENSE00003567109	4189374	4192964
ENSE00003570537	4195553	4195786
ENSE00003673916	4197799	4197915

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 98.88.

FANTOM5 (CAGE): breadth broad, TPM avg 3.6326 / max 502.8239, expressed in 203 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156066	3.5333	194
156067	0.0993	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	98.88	gold quality
gastrocnemius	UBERON:0001388	98.77	gold quality
left ventricle myocardium	UBERON:0006566	98.77	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.70	gold quality
apex of heart	UBERON:0002098	98.69	gold quality
quadriceps femoris	UBERON:0001377	98.50	gold quality
vastus lateralis	UBERON:0001379	98.47	gold quality
heart left ventricle	UBERON:0002084	98.47	gold quality
cardiac ventricle	UBERON:0002082	98.42	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.26	gold quality
skeletal muscle tissue	UBERON:0001134	98.25	gold quality
cardiac atrium	UBERON:0002081	98.11	gold quality
right atrium auricular region	UBERON:0006631	98.11	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.10	gold quality
tibialis anterior	UBERON:0001385	98.08	gold quality
biceps brachii	UBERON:0001507	97.95	gold quality
myocardium	UBERON:0002349	97.64	gold quality
deltoid	UBERON:0001476	97.57	gold quality
muscle of leg	UBERON:0001383	97.32	gold quality
body of tongue	UBERON:0011876	97.25	gold quality
heart right ventricle	UBERON:0002080	96.55	gold quality
heart	UBERON:0000948	96.32	gold quality
muscle tissue	UBERON:0002385	95.53	gold quality
vena cava	UBERON:0004087	94.94	gold quality
tongue	UBERON:0001723	94.10	gold quality
kidney epithelium	UBERON:0004819	92.88	gold quality
nasal cavity epithelium	UBERON:0005384	91.38	gold quality
superior surface of tongue	UBERON:0007371	89.53	gold quality
pharyngeal mucosa	UBERON:0000355	87.83	gold quality
upper arm skin	UBERON:0004263	87.70	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

Upstream regulators (CollecTRI, top): NR1I2, ZNF699

miRNA regulators (miRDB)

105 targeting SRL, 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-513A-5P	100.00	69.77	2465
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-1827	99.63	68.57	3265

Literature-anchored findings (GeneRIF, showing 14)

• KLP61F prevents Ncd-mediated collapse of a nonmicrotubule matrix derived from the interphase nucleus (PMID:15367580)
• Kinesin-5 motors can function by cross-linking and sliding adjacent spindle microtubules without the need for a static spindle matrix. (PMID:18678711)
• results suggest that during morphogenesis of the embryo mitotic spindle, KLP61F’s crosslinking & sliding activities could facilitate accumulation of KLP61F within antiparallel interpolar microtubules at the equator (PMID:19062285)
• KLP61F activity contributes to normal chromosome congression, kinetochore spacing, and anaphase A rates (PMID:19158379)
• calculated the structure of a K5 motor bound to MTs at 9 A resolution, providing insight into this important interaction. (PMID:19285086)
• The work tends to support the “sliding filament” mechanism for KLP61F action in Drosophila embryo spindles. (PMID:19291760)
• Tyrosines in the kinesin-5 (KLP61F)head domain are necessary for phosphorylation by Wee1 and for mitotic spindle integrity. (PMID:19800237)
• A staggered antiparallel coiled-coil ‘BASS’ (bipolar assembly) domain directs the assembly of four kinesin-5 polypeptides into bipolar minifilaments. (PMID:23299893)
• Klp61F knockdown inhibits post-Golgi transport in Drosophila S2 cells. (PMID:23857769)
• Kinesin-5 pauses at microtubule plus ends and enhances polymerization by stabilizing longitudinal tubulin-tubulin interactions. These activities underlie the ability of kinesin-5 to slide and stabilize microtubule bundles in cells. (PMID:26437877)
• KLP61F is required for spindle and centromere symmetry in oocytes. (PMID:27932541)
• Kinesin-5 stabilizes the microtubule network during interphase in syncytial embryos. (PMID:29361546)
• Mislocalization of TORC1 to Lysosomes Caused by KIF11 Inhibition Leads to Aberrant TORC1 Activity. (PMID:32759469)
• Sarcoplasmic Reticulum Ca[2+] Buffer Proteins: A Focus on the Yet-To-Be-Explored Role of Sarcalumenin in Skeletal Muscle Health and Disease. (PMID:36899851)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	srl	ENSDARG00000104587
danio_rerio	SRL	ENSDARG00000112959
mus_musculus	Srl	ENSMUSG00000022519
rattus_norvegicus	Srl	ENSRNOG00000005269
drosophila_melanogaster	CG9297	FBGN0038181

Paralogs (10): EHD3 (ENSG00000013016), EHD2 (ENSG00000024422), EPS15 (ENSG00000085832), EHD4 (ENSG00000103966), EHD1 (ENSG00000110047), EPS15L1 (ENSG00000127527), REPS1 (ENSG00000135597), REPS2 (ENSG00000169891), ITSN2 (ENSG00000198399), ITSN1 (ENSG00000205726)

Protein

Protein identifiers

Sarcalumenin — Q86TD4 (reviewed: Q86TD4)

All UniProt accessions (2): Q86TD4, I3L4D6

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Sarcoplasmic reticulum lumen. Sarcoplasmic reticulum membrane.

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86TD4-2	1	yes
Q86TD4-1	2
Q86TD4-3	3

RefSeq proteins (3): NP_001092284, NP_001310596, NP_001310597 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030381	G_DYNAMIN_dom	Domain
IPR031692	EHD_N	Domain
IPR045063	Dynamin_N	Domain
IPR051943	TRAFAC_Dynamin-like_GTPase	Family

Pfam: PF00350, PF16880

UniProt features (13 total): region of interest 5, splice variant 2, glycosylation site 2, signal peptide 1, chain 1, sequence conflict 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86TD4-F1	84.81	0.61

Functional residue map

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

Glycosylation sites (2): 281, 389

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 79 (showing top): GOBP_MONOATOMIC_CATION_TRANSPORT, CUI_TCF21_TARGETS_2_UP, GOCC_SARCOPLASMIC_RETICULUM_MEMBRANE, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN, GOCC_ENDOPLASMIC_RETICULUM_LUMEN, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_SARCOPLASM, GOCC_ORGANELLE_SUBCOMPARTMENT, GOBP_STORE_OPERATED_CALCIUM_ENTRY, GOCC_SARCOPLASMIC_RETICULUM_LUMEN, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, GSE14386_UNTREATED_VS_IFNA_TREATED_ACT_PBMC_MS_PATIENT_UP, GSE10240_CTRL_VS_IL17_AND_IL22_STIM_PRIMARY_BRONCHIAL_EPITHELIAL_CELLS_DN, MIR651_3P, MIR27A_3P_MIR27B_3P

GO Biological Process (1): store-operated calcium entry (GO:0002115)

GO Molecular Function (2): GTP binding (GO:0005525), protein binding (GO:0005515)

GO Cellular Component (4): sarcoplasmic reticulum membrane (GO:0033017), sarcoplasmic reticulum lumen (GO:0033018), membrane (GO:0016020), sarcoplasmic reticulum (GO:0016529)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sarcoplasmic reticulum	2
calcium ion transport	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
binding	1
endoplasmic reticulum membrane	1
bounding membrane of organelle	1
endoplasmic reticulum lumen	1
cellular anatomical structure	1
endoplasmic reticulum	1
sarcoplasm	1

Protein interactions and networks

STRING

762 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRL	ATP2A1	O14983	756
SRL	CASQ1	P31415	745
SRL	RYR1	P21817	680
SRL	SYPL2	Q5VXT5	619
SRL	TRDN	Q13061	539
SRL	JSRP1	Q96MG2	512
SRL	MYBPC2	Q14324	482
SRL	CALR	P27797	479
SRL	CASQ2	O14958	477
SRL	ATP2A2	P16614	442
SRL	SLN	O00631	433
SRL	ACTN3	Q08043	433
SRL	RGR	P47804	432
SRL	ASPH	Q12797	419
SRL	PYGM	P11217	418

IntAct

5 interactions, top by confidence:

A	B	Type	Score
SRL	PPIB	psi-mi:“MI:0915”(physical association)	0.400
PPP1CA	ACO2	psi-mi:“MI:0914”(association)	0.350
MFGE8	MYH7B	psi-mi:“MI:0914”(association)	0.350
MRPS23	MYH7B	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): SRL (Two-hybrid), SRL (Two-hybrid), SRL (Two-hybrid), SRL (Proximity Label-MS)

ESM2 similar proteins: A0A8I3S9V6, A0M8U1, A6NH52, E1BWM5, O35089, P13666, P86050, Q00765, Q0VCK9, Q0X0A5, Q1RLU8, Q29S14, Q2PG42, Q3KNM2, Q3ZC24, Q5BJU5, Q5M7T4, Q5R9I4, Q5R9K4, Q5RE33, Q5T4T1, Q5ZJ41, Q5ZJD7, Q6DD32, Q6GM44, Q6NYF1, Q6P360, Q6PI25, Q7TQ48, Q86TD4, Q8C407, Q8L5Y9, Q8MK44, Q8R1Z9, Q91ZQ0, Q940S0, Q96GC9, Q99K70, Q99KU0, Q9BSR8

Diamond homologs: A3LN86, B3LF48, O42287, P13666, P42566, P42567, Q10172, Q15811, Q4V8H8, Q54KI4, Q5AHB1, Q5E9R3, Q5RBP4, Q60902, Q641Z6, Q7TQ48, Q80XA6, Q86TD4, Q8BH64, Q8R491, Q90577, Q94CF0, Q9EQP2, Q9H223, Q9H4M9, Q9HGL2, Q9NZM3, Q9NZN3, Q9NZN4, Q9QXY6, Q9UBC2, Q9WVE9, Q9WVK4, Q9Z0R4, Q9Z0R6, A1CD74, A1CPG1, A1D2B8, A1DC51, A1DDY6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	65
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
688768	GRCh37/hg19 16p13.3(chr16:3469027-4328143)x3	Pathogenic

SpliceAI

1505 predictions. Top by Δscore:

Variant	Effect	Δscore
16:4192962:AGC:A	acceptor_gain	1.0000
16:4192964:CC:C	acceptor_loss	1.0000
16:4192964:CCTT:C	acceptor_gain	1.0000
16:4192965:C:CC	acceptor_gain	1.0000
16:4192965:CTTT:C	acceptor_loss	1.0000
16:4192966:T:C	acceptor_gain	1.0000
16:4195548:ATTAC:A	donor_loss	1.0000
16:4195549:TTA:T	donor_loss	1.0000
16:4195550:TAC:T	donor_loss	1.0000
16:4195551:ACCTC:A	donor_loss	1.0000
16:4195552:C:A	donor_loss	1.0000
16:4195552:CCT:C	donor_gain	1.0000
16:4203161:CCTA:C	donor_loss	1.0000
16:4203163:TAC:T	donor_loss	1.0000
16:4203165:C:G	donor_loss	1.0000
16:4203259:CCG:C	acceptor_gain	1.0000
16:4203260:CG:C	acceptor_gain	1.0000
16:4203260:CGC:C	acceptor_gain	1.0000
16:4203262:C:CC	acceptor_gain	1.0000
16:4204523:C:A	donor_gain	1.0000
16:4204528:GTTAC:G	donor_loss	1.0000
16:4204529:TTA:T	donor_loss	1.0000
16:4204530:TA:T	donor_loss	1.0000
16:4204531:A:C	donor_loss	1.0000
16:4204556:T:TA	donor_gain	1.0000
16:4204630:CTCTT:C	acceptor_gain	1.0000
16:4204632:CTT:C	acceptor_gain	1.0000
16:4204633:TT:T	acceptor_gain	1.0000
16:4204635:C:CC	acceptor_gain	1.0000
16:4204636:T:G	acceptor_loss	1.0000

AlphaMissense

3131 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:4192391:A:G	L395P	1.000
16:4192553:C:G	R341P	1.000
16:4192566:C:G	A337P	1.000
16:4192755:A:G	W274R	1.000
16:4192755:A:T	W274R	1.000
16:4192760:A:G	L272P	1.000
16:4192814:A:G	L254P	1.000
16:4195645:A:G	L173P	1.000
16:4195721:C:G	G148R	1.000
16:4195756:A:T	V136D	1.000
16:4197855:G:A	S107F	1.000
16:4197861:C:T	G105D	1.000
16:4197871:A:G	W102R	1.000
16:4197871:A:T	W102R	1.000
16:4197877:C:G	G100R	1.000
16:4197877:C:T	G100R	1.000
16:4192394:T:C	D394G	0.999
16:4192402:G:C	S391R	0.999
16:4192402:G:T	S391R	0.999
16:4192404:T:G	S391R	0.999
16:4192406:A:T	V390D	0.999
16:4192527:A:C	Y350D	0.999
16:4192535:A:T	V347D	0.999
16:4192538:A:G	L346P	0.999
16:4192541:A:G	L345P	0.999
16:4192544:G:T	A344D	0.999
16:4192545:C:G	A344P	0.999
16:4192556:A:T	V340D	0.999
16:4192565:G:T	A337D	0.999
16:4192568:T:G	H336P	0.999

dbSNP variants (sampled 300 via entrez): RS1000162756 (16:4208799 T>C), RS1000181349 (16:4219394 C>T), RS1000196951 (16:4217140 G>C), RS1000223033 (16:4204696 C>A), RS1000334291 (16:4225534 T>G), RS1000360462 (16:4213571 C>T), RS1000375375 (16:4225685 G>A), RS1000403291 (16:4242495 A>T), RS1000445346 (16:4189258 G>A), RS1000461214 (16:4239033 G>A,T), RS1000465270 (16:4189516 C>G), RS1000473877 (16:4221324 G>A), RS1000525053 (16:4212507 A>C), RS1000535922 (16:4216110 C>G,T), RS1000610249 (16:4205718 G>A,C)

Disease associations

OMIM: gene MIM:604992 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

48 associations (top):

Study	Trait	p-value
GCST001762_661	Obesity-related traits	5.000000e-06
GCST002500_44	QT interval	9.000000e-07
GCST006585_1701	Blood protein levels	6.000000e-10
GCST009391_1369	Metabolite levels	9.000000e-06
GCST010320_30	PR interval	2.000000e-09
GCST010321_50	PR interval	2.000000e-10
GCST010703_267	Brain morphology (MOSTest)	4.000000e-13
GCST010796_100	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_26	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_27	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-10
GCST010796_28	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-09
GCST010796_29	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_30	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-09
GCST010796_31	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-10
GCST010796_32	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_33	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-09
GCST010796_34	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_35	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-10
GCST010796_356	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-09
GCST010796_36	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-10
GCST010796_37	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST010796_38	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-09
GCST010796_39	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-09
GCST010796_40	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_41	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST010796_42	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-10
GCST010796_43	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-10
GCST010796_44	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-10
GCST010796_45	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-09
GCST010796_46	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-09

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0005188	CCL11 measurement
EFO:0004682	QT interval
EFO:0010366	lysophosphatidylethanolamine 16:0 measurement
EFO:0004462	PR interval
EFO:0004346	neuroimaging measurement
EFO:0004327	electrocardiography
EFO:0008039	BMI-adjusted hip circumference
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Doxorubicin	decreases expression	2
aristolochic acid I	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
ophiopogonin D	decreases expression	1
bisphenol S	decreases methylation	1
incobotulinumtoxinA	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Arsenic	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Methapyrilene	decreases methylation	1
Nickel	decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1
1-Methyl-4-phenylpyridinium	increases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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