FSD1L

Summary

FSD1L (fibronectin type III and SPRY domain containing 1 like, HGNC:13753) is a protein-coding gene on chromosome 9q31.2, encoding FSD1-like protein (Q9BXM9).

Predicted to be located in membrane.

Source: NCBI Gene 83856 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 65 total — 1 pathogenic
• MANE Select transcript: NM_001145313

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13753
Approved symbol	FSD1L
Name	fibronectin type III and SPRY domain containing 1 like
Location	9q31.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000106701
Ensembl biotype	protein_coding
OMIM	609829
Entrez	83856

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000374707, ENST00000394926, ENST00000469022, ENST00000480279, ENST00000481272, ENST00000484973, ENST00000495708, ENST00000955870, ENST00000955871

RefSeq mRNA: 5 — MANE Select: NM_001145313 NM_001145313, NM_001287191, NM_001287192, NM_001330739, NM_031919

CCDS: CCDS47999, CCDS6764, CCDS6765, CCDS83391

Canonical transcript exons

ENST00000481272 — 14 exons

Exon	Start	End
ENSE00000983369	105508617	105508715
ENSE00000983371	105534493	105534593
ENSE00000983372	105535067	105535318
ENSE00000983373	105539263	105539351
ENSE00001464400	105546358	105552433
ENSE00001520028	105512807	105512936
ENSE00001786442	105461520	105461615
ENSE00002245215	105448034	105448235
ENSE00003565929	105506399	105506608
ENSE00003569864	105479354	105479376
ENSE00003575289	105468193	105468324
ENSE00003608033	105464236	105464331
ENSE00003670837	105471904	105472005
ENSE00003677945	105484381	105484502

Expression profiles

Bgee: expression breadth ubiquitous, 227 present calls, max score 95.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.3705 / max 293.1452, expressed in 1628 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97840	8.2960	1609
97843	1.3796	117
97842	0.4915	93
97841	0.2034	86

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	95.73	gold quality
cortical plate	UBERON:0005343	93.35	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.37	gold quality
ventricular zone	UBERON:0003053	90.14	gold quality
substantia nigra pars compacta	UBERON:0001965	88.86	gold quality
ganglionic eminence	UBERON:0004023	88.22	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	87.60	gold quality
bronchial epithelial cell	CL:0002328	87.45	gold quality
deltoid	UBERON:0001476	87.28	gold quality
biceps brachii	UBERON:0001507	86.08	gold quality
bronchus	UBERON:0002185	85.99	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.78	gold quality
middle temporal gyrus	UBERON:0002771	85.37	gold quality
tibialis anterior	UBERON:0001385	85.25	gold quality
Brodmann (1909) area 46	UBERON:0006483	84.73	gold quality
mucosa of paranasal sinus	UBERON:0005030	84.68	gold quality
primary visual cortex	UBERON:0002436	84.48	gold quality
substantia nigra pars reticulata	UBERON:0001966	84.17	gold quality
sperm	CL:0000019	83.98	gold quality
pigmented layer of retina	UBERON:0001782	83.78	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.70	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	83.27	gold quality
skeletal muscle tissue	UBERON:0001134	83.20	gold quality
spinal cord	UBERON:0002240	82.95	gold quality
oviduct epithelium	UBERON:0004804	82.43	gold quality
lateral nuclear group of thalamus	UBERON:0002736	82.28	gold quality
superior frontal gyrus	UBERON:0002661	82.19	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.07	gold quality
dorsal root ganglion	UBERON:0000044	82.04	gold quality
entorhinal cortex	UBERON:0002728	82.04	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	24.83
E-ANND-3	yes	5.34
E-GEOD-137537	no	3.66

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• significant internalisation of type 2 cystatins from the extracellular to intracellular compartments (PMID:20800088)
• Maternal glycemia in pregnancy is longitudinally associated with blood DNAm variation at the FSD1L gene from birth to 5 years of age. (PMID:37386647)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fsd1l	ENSDARG00000059432
mus_musculus	Fsd1l	ENSMUSG00000054752
rattus_norvegicus	Fsd1l	ENSRNOG00000059876

Paralogs (3): FSD1 (ENSG00000105255), CMYA5 (ENSG00000164309), FSD2 (ENSG00000186628)

Protein

Protein identifiers

FSD1-like protein — Q9BXM9 (reviewed: Q9BXM9)

Alternative names: Coiled-coil domain-containing protein 10, FSD1 N-terminal-like protein

All UniProt accessions (5): Q9BXM9, A0A0C4DG97, C9JD05, F8W946, Q8N450

UniProt curated annotations — full annotation on UniProt →

Miscellaneous. Due to intron retention.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BXM9-1	1	yes
Q9BXM9-2	2
Q9BXM9-3	3

RefSeq proteins (5): NP_001138785, NP_001274120, NP_001274121, NP_001317668, NP_114125 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001870	B30.2/SPRY	Domain
IPR003649	Bbox_C	Domain
IPR003877	SPRY_dom	Domain
IPR003879	Butyrophylin_SPRY	Domain
IPR003961	FN3_dom	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR017903	COS_domain	Domain
IPR035742	SPRY/PRY_FSD1	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR050617	E3_ligase_FN3/SPRY	Family

Pfam: PF00041, PF00622

UniProt features (17 total): modified residue 4, domain 3, splice variant 3, sequence conflict 2, compositionally biased region 2, chain 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXM9-F1	85.09	0.70

Functional residue map

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

Post-translational modifications (4): 1, 1, 520, 523

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 170 (showing top): GTGCCTT_MIR506, BIDUS_METASTASIS_UP, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, COLDREN_GEFITINIB_RESISTANCE_UP, JOHNSTONE_PARVB_TARGETS_2_DN, HMG20B_TARGET_GENES, RYBP_TARGET_GENES, SKIL_TARGET_GENES, TAFAZZIN_TARGET_GENES, ZNF597_TARGET_GENES, MIR607, MIR3646, MIR1277_5P, MIR651_3P, MIR5696

GO Biological Process (1): biological_process (GO:0008150)

GO Molecular Function (2): molecular_function (GO:0003674), protein binding (GO:0005515)

GO Cellular Component (2): cellular_component (GO:0005575), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

312 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FSD1L	TUBG1	P23258	549
FSD1L	BBOX1	O75936	541
FSD1L	FN1	P02751	524
FSD1L	CDK5	Q00535	443
FSD1L	TMEM38B	Q9NVV0	417
FSD1L	FKTN	O75072	414
FSD1L	UPF3B	Q9BZI7	367
FSD1L	PDRG1	Q9NUG6	355
FSD1L	SLC25A17	O43808	353
FSD1L	SLC44A1	Q8WWI5	344
FSD1L	TAL2	Q16559	337
FSD1L	PCYOX1	Q9UHG3	334
FSD1L	RNF207	Q6ZRF8	331
FSD1L	NIPSNAP3A	Q9UFN0	324
FSD1L	ZNF99	A8MXY4	320

IntAct

3 interactions, top by confidence:

A	B	Type	Score
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
FSD1L	rne	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): FSD1L (Affinity Capture-MS), FSD1L (Affinity Capture-MS), FSD1L (Affinity Capture-MS), FSD1L (Affinity Capture-MS), FSD1L (Affinity Capture-MS), KIAA0895 (Cross-Linking-MS (XL-MS)), FSD1L (Affinity Capture-RNA), APP (Reconstituted Complex), FSD1L (Affinity Capture-Luminescence)

ESM2 similar proteins: A0A3L7I2I8, A4IF63, A4II46, A6QQZ7, A8KBF6, D2GXS7, D3ZQG6, D3ZVM4, E1BJS7, E7FAM5, F6QEU4, F7H9X2, O60733, O70277, O75382, P23727, P26450, P27986, P42694, P49754, P79987, P97570, P97819, Q15139, Q1LY10, Q1PRL4, Q1PSW8, Q28C55, Q2Q1W2, Q2T9K6, Q59H18, Q5GIG6, Q5R685, Q5RF15, Q5T2T1, Q5U2Y3, Q63787, Q7TQP6, Q8AVG0, Q8BVD5

Diamond homologs: A0A2P1BRP3, A0A2P1BRQ0, A0ZSK3, A0ZSK4, O70583, O95361, Q05B84, Q14258, Q1XHU0, Q309B1, Q4R539, Q5R760, Q61510, Q6MFZ5, Q7TPM6, Q8BVW3, Q8BYN5, Q91453, Q98989, Q98993, Q99PP9, Q9BTV5, Q9BXM9, Q9ESN2, Q9HCM9, Q9Y577, A0JN74, A4QPC6, A6NGJ6, A6NI03, A6NK02, A6NLI5, A6NLU0, B1H278, C9J1S8, F4I443, F8VTS6, O00478, O00481, O15344

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	50
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2628091	NM_001145313.3(FSD1L):c.1411C>T (p.Gln471Ter)	Pathogenic

SpliceAI

2396 predictions. Top by Δscore:

Variant	Effect	Δscore
9:105448232:GAAA:G	donor_gain	1.0000
9:105448233:A:T	donor_gain	1.0000
9:105448236:G:GG	donor_gain	1.0000
9:105461470:A:AG	acceptor_gain	1.0000
9:105461477:T:TA	acceptor_gain	1.0000
9:105461482:T:TA	acceptor_gain	1.0000
9:105464229:A:G	acceptor_gain	1.0000
9:105464231:TCTA:T	acceptor_loss	1.0000
9:105464233:TA:T	acceptor_loss	1.0000
9:105464234:A:AG	acceptor_gain	1.0000
9:105464234:AG:A	acceptor_gain	1.0000
9:105464235:G:GT	acceptor_gain	1.0000
9:105464235:GG:G	acceptor_gain	1.0000
9:105464235:GGA:G	acceptor_gain	1.0000
9:105464235:GGAA:G	acceptor_gain	1.0000
9:105464327:TTCAG:T	donor_loss	1.0000
9:105464328:TCAG:T	donor_loss	1.0000
9:105464329:CAGG:C	donor_loss	1.0000
9:105464330:AG:A	donor_loss	1.0000
9:105464331:GGTAT:G	donor_loss	1.0000
9:105464332:GT:G	donor_loss	1.0000
9:105464333:T:A	donor_loss	1.0000
9:105468187:A:AG	acceptor_gain	1.0000
9:105468188:A:G	acceptor_gain	1.0000
9:105468191:A:AG	acceptor_gain	1.0000
9:105468191:AG:A	acceptor_gain	1.0000
9:105468191:AGG:A	acceptor_loss	1.0000
9:105468192:G:A	acceptor_loss	1.0000
9:105468192:G:GT	acceptor_gain	1.0000
9:105468192:GG:G	acceptor_gain	1.0000

AlphaMissense

3521 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:105506464:T:A	W218R	1.000
9:105506464:T:C	W218R	1.000
9:105512849:T:C	L313P	1.000
9:105512875:T:A	W322R	1.000
9:105512875:T:C	W322R	1.000
9:105512877:G:C	W322C	1.000
9:105512877:G:T	W322C	1.000
9:105534566:T:C	F367L	1.000
9:105534567:T:C	F367S	1.000
9:105534568:T:A	F367L	1.000
9:105534568:T:G	F367L	1.000
9:105535099:T:A	W387R	1.000
9:105535099:T:C	W387R	1.000
9:105535141:G:A	G401R	1.000
9:105535141:G:C	G401R	1.000
9:105535142:G:A	G401E	1.000
9:105535180:G:A	G414R	1.000
9:105535180:G:C	G414R	1.000
9:105535181:G:A	G414E	1.000
9:105535181:G:T	G414V	1.000
9:105535195:A:C	S419R	1.000
9:105535197:T:A	S419R	1.000
9:105535197:T:G	S419R	1.000
9:105535198:T:A	W420R	1.000
9:105535198:T:C	W420R	1.000
9:105535219:T:A	W427R	1.000
9:105535219:T:C	W427R	1.000
9:105535221:G:C	W427C	1.000
9:105535221:G:T	W427C	1.000
9:105471961:G:C	A133P	0.999

dbSNP variants (sampled 300 via entrez): RS1000008526 (9:105456670 AT>A,ATT), RS1000027140 (9:105450329 G>A), RS1000078968 (9:105449951 T>A), RS1000079235 (9:105533267 A>G), RS1000126652 (9:105499709 C>A,T), RS1000133067 (9:105533101 T>G), RS1000134484 (9:105486485 T>C,G), RS1000171663 (9:105468796 A>G), RS1000224791 (9:105478593 G>GT), RS1000254835 (9:105456528 G>A,C), RS1000278499 (9:105478953 G>A), RS1000309519 (9:105450692 C>T), RS1000367687 (9:105527671 A>G), RS1000405536 (9:105456364 G>A), RS1000440515 (9:105522295 A>T)

Disease associations

OMIM: gene MIM:609829 | disease phenotypes: MIM:236600

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal recessive

Mondo (2): hydrocephalus, nonsyndromic, autosomal recessive 1 (MONDO:0009360), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): Congenital hydrocephalus (Orphanet:2185)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000404_1	Menarche (age at onset)	2.000000e-09
GCST008163_570	Height	2.000000e-06
GCST009391_1392	Metabolite levels	7.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0010368	lysophosphatidylethanolamine 18:1 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

53 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	6
trichostatin A	affects cotreatment, decreases expression	2
Air Pollutants	increases abundance, increases expression, affects cotreatment, decreases expression	2
Particulate Matter	decreases expression, decreases reaction, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
TL8-506	affects cotreatment, increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	decreases expression, increases abundance, affects cotreatment	1
salinomycin	decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
ochratoxin A	decreases expression	1
cupric oxide	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
pentabromodiphenyl ether	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
entinostat	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
torcetrapib	increases expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
incobotulinumtoxinA	decreases expression	1
Bortezomib	increases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice