SAMD9L

Summary

SAMD9L (sterile alpha motif domain containing 9 like, HGNC:1349) is a protein-coding gene on chromosome 7q21.2, encoding Sterile alpha motif domain-containing protein 9-like (Q8IVG5). May be involved in endosome fusion.

This gene encodes a cytoplasmic protein that acts as a tumor suppressor but also plays a key role in cell proliferation and the innate immune response to viral infection. The encoded protein contains an N-terminal sterile alpha motif domain. Naturally occurring mutations in this gene are associated with myeloid disorders such as juvenile myelomonocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome. Naturally occurring mutations are also associated with hepatitis-B related hepatocellular carcinoma, normophosphatemic familial tumoral calcinosis, and ataxia-pancytopenia syndrome.

Source: NCBI Gene 219285 — RefSeq curated summary.

At a glance

• Gene–disease (curated): SAMD9L-related spectrum and myeloid neoplasm risk (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 2,453 total — 4 pathogenic, 14 likely-pathogenic
• Phenotypes (HPO): 48
• MANE Select transcript: NM_152703

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1349
Approved symbol	SAMD9L
Name	sterile alpha motif domain containing 9 like
Location	7q21.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA2005, FLJ39885
Ensembl gene	ENSG00000177409
Ensembl biotype	protein_coding
OMIM	611170
Entrez	219285

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000318238, ENST00000411955, ENST00000414791, ENST00000437805, ENST00000439952, ENST00000446033, ENST00000446959, ENST00000477816, ENST00000699641, ENST00000962867

RefSeq mRNA: 9 — MANE Select: NM_152703 NM_001303496, NM_001303497, NM_001303498, NM_001303500, NM_001350082, NM_001350083, NM_001350084, NM_001350085, NM_152703

CCDS: CCDS34681

Canonical transcript exons

ENST00000318238 — 5 exons

Exon	Start	End
ENSE00001277824	93130056	93135991
ENSE00001297947	93146883	93147146
ENSE00001301161	93144732	93144833
ENSE00001317826	93145385	93146040
ENSE00001929348	93148194	93148385

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 93.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.6938 / max 1938.2201, expressed in 1231 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84859	14.2065	1222
84857	0.2402	96
84856	0.2103	93
84858	0.0368	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	93.76	gold quality
buccal mucosa cell	CL:0002336	92.93	gold quality
leukocyte	CL:0000738	92.20	gold quality
monocyte	CL:0000576	92.18	gold quality
granulocyte	CL:0000094	91.24	gold quality
bone marrow cell	CL:0002092	91.21	gold quality
vermiform appendix	UBERON:0001154	91.04	gold quality
colonic epithelium	UBERON:0000397	90.61	gold quality
decidua	UBERON:0002450	90.49	gold quality
calcaneal tendon	UBERON:0003701	90.46	gold quality
ileal mucosa	UBERON:0000331	88.90	gold quality
palpebral conjunctiva	UBERON:0001812	88.86	gold quality
epithelium of nasopharynx	UBERON:0001951	88.70	gold quality
blood	UBERON:0000178	88.47	gold quality
spleen	UBERON:0002106	88.10	gold quality
lymph node	UBERON:0000029	87.46	gold quality
epithelial cell of pancreas	CL:0000083	87.08	gold quality
tendon	UBERON:0000043	86.25	gold quality
amniotic fluid	UBERON:0000173	86.15	gold quality
visceral pleura	UBERON:0002401	85.92	gold quality
caecum	UBERON:0001153	84.91	gold quality
rectum	UBERON:0001052	84.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.43	gold quality
gall bladder	UBERON:0002110	84.40	gold quality
bone marrow	UBERON:0002371	83.94	gold quality
smooth muscle tissue	UBERON:0001135	83.24	gold quality
tibialis anterior	UBERON:0001385	83.20	silver quality
thymus	UBERON:0002370	83.10	gold quality
parietal pleura	UBERON:0002400	82.87	gold quality
right lung	UBERON:0002167	82.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-53	yes	1143.38
E-ANND-3	yes	5.61

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP63

miRNA regulators (miRDB)

70 targeting SAMD9L, 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-6867-5P	100.00	82.21	3464
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-580-3P	99.67	69.23	1841

Literature-anchored findings (GeneRIF, showing 21)

• The findings highlight a novel tumor-suppressive role of SAMD9L inactivation by somatic mutation and decreased expression in human HBV-related HCC (PMID:25076857)
• Missense Mutations in SAMD9L gene is Associated with Ataxia-Pancytopenia Syndrome. (PMID:27259050)
• Gain-of-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms in two unrelated Caucasian families. (PMID:28202457)
• Constitutional mutations (p.H880Q, p.R986H, p.R986C and p.V1512M) in the SAMD9L gene on 7q21 define a new subtype of familial myelodysplastic syndrome and provide an explanation for the phenomenon of transient monosomy 7. (PMID:29217778)
• In humans, both SAMD9 and SAMD9L are poxvirus restriction factors, although the latter requires interferon induction in many cell types. (PMID:29447249)
• REVIEW: expert-based recommendations regarding diagnosis, follow-up, and treatment of mutation carriers. (PMID:29535429)
• SAMD9 and SAMD9L germline loss-of-function variants exist in 3% of adult myelodysplastic syndromes and are located more in the N terminus relative to pediatric germline loss-of-function variants, which exist more in the C terminus. (PMID:30322869)
• Germline SAMD9L mutation is associated with ataxia-pancytopenia syndrome and pediatric acute lymphoblastic leukemia. (PMID:30923096)
• Identification of SAMD9L as a susceptibility locus for intravenous immunoglobulin resistance in Kawasaki disease by genome-wide association analysis. (PMID:30971808)
• Prevalence of germline GATA2 and SAMD9/9L variants in paediatric haematological disorders with monosomy 7. (PMID:32770553)
• Germline predisposition in myeloid neoplasms: Unique genetic and clinical features of GATA2 deficiency and SAMD9/SAMD9L syndromes. (PMID:33038986)
• Multiorgan failure with abnormal receptor metabolism in mice mimicking Samd9/9L syndromes. (PMID:33373325)
• Pediatric MDS and bone marrow failure-associated germline mutations in SAMD9 and SAMD9L impair multiple pathways in primary hematopoietic cells. (PMID:33731850)
• SAMD9L autoinflammatory or ataxia pancytopenia disease mutations activate cell-autonomous translational repression. (PMID:34417303)
• Clinical evolution, genetic landscape and trajectories of clonal hematopoiesis in SAMD9/SAMD9L syndromes. (PMID:34621053)
• Up-regulated SAMD9L modulated by TLR2 and HIF-1alpha as a promising biomarker in tuberculosis. (PMID:35388602)
• Clonal Elimination of the Pathogenic Allele as Diagnostic Pitfall in SAMD9L-Associated Neuropathy. (PMID:36553623)
• Viral host range factors antagonize pathogenic SAMD9 and SAMD9L variants. (PMID:36894052)
• Functional Study of SAMD9L in Familial Gastric Cancer. (PMID:37158533)
• [Pancytopenia in children caused by SAMD9/9L mutation: 5 cases report and literature review]. (PMID:37357006)
• PARP14 correlates with GBM proliferation and poor prognosis by elevating expression of SAMD/SAMD9L. (PMID:37612499)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	SAMD9	ENSDARG00000102729
mus_musculus	Samd9l	ENSMUSG00000047735
rattus_norvegicus	Samd9l	ENSRNOG00000063679

Paralogs (1): SAMD9 (ENSG00000205413)

Protein

Protein identifiers

Sterile alpha motif domain-containing protein 9-like — Q8IVG5 (reviewed: Q8IVG5)

All UniProt accessions (2): Q8IVG5, A0A0B4J1Y6

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in endosome fusion. Mediates down-regulation of growth factor signaling via internalization of growth factor receptors.

Subunit / interactions. Interacts with EEA1.

Subcellular location. Early endosome. Mitochondrion.

Tissue specificity. Widely expressed in adult and fetal tissues. Expressed in the cerebellum. Variable expression in tumors. Down-regulated in breast cancer.

Disease relevance. Ataxia-pancytopenia syndrome (ATXPC) [MIM:159550] An autosomal dominant disorder characterized by cerebellar ataxia, variable hematologic cytopenias, and predisposition to bone marrow failure and myeloid leukemia. The disease is caused by variants affecting the gene represented in this entry. Monosomy 7 myelodysplasia and leukemia syndrome 1 (M7MLS1) [MIM:252270] A hematologic disorder characterized by bone marrow dyspoiesis and pancytopenia manifesting in early childhood, associated with monosomy 7 in the bone marrow. Disease severity ranges from transient thrombocytopenia or anemia, or normal peripheral blood counts with transient bone marrow abnormalities or transient monosomy 7, to frank myelodysplastic syndrome or acute myelogenous leukemia. M7MLS1 inheritance is autosomal dominant with incomplete penetrance and variable expressivity. The disease is caused by variants affecting the gene represented in this entry. Germline variants in SAMD9L with a suppressive effect on the cell cycle are associated with somatic loss of the chromosome 7 harboring the mutant allele. This results in the deletion of several genes and predisposes to the development of myelodysplastic syndrome and acute myelogenous leukemia. Spinocerebellar ataxia 49 (SCA49) [MIM:619806] A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA49 is an autosomal dominant, slowly progressive form characterized by ataxia, nystagmus, dysarthria, polyneuropathy, pyramidal signs, cerebellar atrophy and distinctive cerebral demyelination. Affected individuals present with horizontal and vertical gaze-evoked nystagmus and hyperreflexia as initial clinical signs. Age of disease onset ranges from the second to seventh decades, even within the same family. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Dubious isoform produced through aberrant splice sites.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IVG5-1	1	yes
Q8IVG5-2	2, UEF3

RefSeq proteins (9): NP_001290425, NP_001290426, NP_001290427, NP_001290429, NP_001337011, NP_001337012, NP_001337013, NP_001337014, NP_689916* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001660	SAM	Domain
IPR013761	SAM/pointed_sf	Homologous_superfamily

UniProt features (15 total): sequence variant 10, chain 1, domain 1, region of interest 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IVG5-F1	83.85	0.50

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 330 (showing top): GOZGIT_ESR1_TARGETS_DN, YORDY_RECIPROCAL_REGULATION_BY_ETS1_AND_SP100_DN, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP, COWLING_MYCN_TARGETS, SANA_TNF_SIGNALING_UP, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_WITH_LMP1_UP, LI_INDUCED_T_TO_NATURAL_KILLER_UP, CHICAS_RB1_TARGETS_CONFLUENT, GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_DN, PEDRIOLI_MIR31_TARGETS_DN, BOSCO_INTERFERON_INDUCED_ANTIVIRAL_MODULE, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): cytoplasm (GO:0005737), mitochondrion (GO:0005739), early endosome (GO:0005769), endosome (GO:0005768)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1
endosome	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

1588 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SAMD9L	HEPACAM2	A8MVW5	620
SAMD9L	IFIT3	O14879	616
SAMD9L	IFI44	Q8TCB0	609
SAMD9L	IFIT2	P09913	586
SAMD9L	USP18	Q9UMW8	561
SAMD9L	EPSTI1	Q96J88	520
SAMD9L	STAT1	P42224	517
SAMD9L	LEF1	Q9UJU2	503
SAMD9L	RIGI	O95786	501
SAMD9L	EPHB2	P29323	497
SAMD9L	IFIH1	Q9BYX4	497
SAMD9L	GBP2	P32456	492
SAMD9L	ERCC6L2	Q5T890	482
SAMD9L	ANKRD26	Q9UPS8	469
SAMD9L	KATNA1	O75449	463

IntAct

7 interactions, top by confidence:

A	B	Type	Score
EEA1	SAMD9L	psi-mi:“MI:0915”(physical association)	0.400
SAMD9L		psi-mi:“MI:0915”(physical association)	0.370
BCAR1	CEP290	psi-mi:“MI:0914”(association)	0.350
APBB1	SSPOP	psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
SAMD9L	rhaB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): SAMD9L (Biochemical Activity), SAMD9L (Affinity Capture-MS), SAMD9L (Synthetic Lethality), SAMD9L (Affinity Capture-MS), SAMD9L (Affinity Capture-RNA), SAMD9L (Affinity Capture-RNA), SAMD9L (Affinity Capture-MS), SAMD9L (Cross-Linking-MS (XL-MS)), HNRNPA1 (Cross-Linking-MS (XL-MS)), HNRNPA1L2 (Cross-Linking-MS (XL-MS)), DCTN1 (Cross-Linking-MS (XL-MS)), ENO1 (Cross-Linking-MS (XL-MS)), SAMD9L (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GW35, A6QNM3, B0R034, B1ANS9, B9EK06, D2KC46, D3ZY60, F1MS15, F1P065, F1REV3, O00522, O15091, O75747, P10911, P58069, Q008S8, Q14449, Q14D04, Q15283, Q32NR9, Q45GW3, Q4R366, Q4R6T7, Q5H9U9, Q5K651, Q5PQS3, Q5XGX5, Q5XIZ9, Q5ZLD2, Q60862, Q63713, Q69Z37, Q6DCF6, Q6S5J6, Q6TNJ1, Q75PQ8, Q80W71, Q86VD1, Q86YR7, Q8C5W4

Diamond homologs: Q52KW0, Q5K651, Q69Z37, Q8IVG5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

2453 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	14
Uncertain significance	1658
Likely benign	644
Benign	13

Top pathogenic / likely-pathogenic (18)

Variant ID	HGVS	Classification
1319843	NM_152703.5(SAMD9L):c.4534G>A (p.Val1512Met)	Pathogenic
242372	NM_152703.5(SAMD9L):c.2640C>A (p.His880Gln)	Pathogenic
446529	NM_152703.5(SAMD9L):c.2672T>C (p.Ile891Thr)	Pathogenic
988631	NM_152703.5(SAMD9L):c.3842G>A (p.Arg1281Lys)	Pathogenic
1184844	NM_152703.5(SAMD9L):c.2658_2659del (p.Phe886fs)	Likely pathogenic
1209111	NM_152703.5(SAMD9L):c.2682_2690delinsAAATTTGG (p.Ser894fs)	Likely pathogenic
1320284	NM_152703.5(SAMD9L):c.4654T>A (p.Tyr1552Asn)	Likely pathogenic
1333474	NM_152703.5(SAMD9L):c.303del (p.Asn103fs)	Likely pathogenic
2418948	NM_152703.5(SAMD9L):c.4418G>A (p.Ser1473Asn)	Likely pathogenic
2445760	NM_152703.5(SAMD9L):c.2062T>A (p.Tyr688Asn)	Likely pathogenic
3239554	NM_152703.5(SAMD9L):c.2309del (p.Lys770fs)	Likely pathogenic
3340782	NM_152703.5(SAMD9L):c.3538T>C (p.Trp1180Arg)	Likely pathogenic
3382574	NM_152703.5(SAMD9L):c.2675T>G (p.Met892Arg)	Likely pathogenic
3897221	NM_152703.5(SAMD9L):c.2308A>G (p.Lys770Glu)	Likely pathogenic
4056350	NM_152703.5(SAMD9L):c.1618A>G (p.Arg540Gly)	Likely pathogenic
624285	NM_152703.5(SAMD9L):c.658G>A (p.Glu220Lys)	Likely pathogenic
981905	NM_152703.5(SAMD9L):c.2722A>G (p.Ile908Val)	Likely pathogenic
983121	NM_152703.5(SAMD9L):c.2905A>G (p.Thr969Ala)	Likely pathogenic

SpliceAI

769 predictions. Top by Δscore:

Variant	Effect	Δscore
7:93145950:T:A	donor_gain	1.0000
7:93145971:T:TA	donor_gain	1.0000
7:93148190:TTACC:T	donor_loss	1.0000
7:93148191:TAC:T	donor_loss	1.0000
7:93148192:A:AC	donor_gain	1.0000
7:93148192:AC:A	donor_gain	1.0000
7:93148192:ACCA:A	donor_loss	1.0000
7:93148193:C:A	donor_loss	1.0000
7:93148193:C:CC	donor_gain	1.0000
7:93148193:CC:C	donor_gain	1.0000
7:93148193:CCA:C	donor_gain	1.0000
7:93148193:CCAG:C	donor_gain	1.0000
7:93148193:CCAGG:C	donor_gain	1.0000
7:93135990:TCCT:T	acceptor_loss	0.9900
7:93135991:CCTGA:C	acceptor_loss	0.9900
7:93135992:CTGAG:C	acceptor_loss	0.9900
7:93135993:T:G	acceptor_loss	0.9900
7:93145582:T:C	acceptor_gain	0.9900
7:93145592:CGTAT:C	acceptor_gain	0.9900
7:93145593:G:C	acceptor_gain	0.9900
7:93145596:T:TC	acceptor_gain	0.9900
7:93145600:A:C	acceptor_gain	0.9900
7:93145918:C:CT	donor_gain	0.9900
7:93145919:T:TT	donor_gain	0.9900
7:93145938:T:TA	donor_gain	0.9900
7:93145599:C:CT	acceptor_gain	0.9800
7:93145944:T:C	donor_gain	0.9800
7:93135988:CTTC:C	acceptor_gain	0.9700
7:93135992:C:CC	acceptor_gain	0.9700
7:93145593:G:GC	acceptor_gain	0.9700

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000141316 (7:93132467 G>A,T), RS1000357874 (7:93139841 C>G,T), RS1000486439 (7:93144169 A>G), RS1000818734 (7:93142655 T>G), RS1001283971 (7:93130060 T>A), RS1001516801 (7:93145850 T>C), RS1001697492 (7:93130312 G>A), RS1001828193 (7:93137923 A>T), RS1001842148 (7:93143351 G>C), RS1001939428 (7:93138256 G>A), RS1001956828 (7:93145117 A>C,G), RS1002094154 (7:93145570 C>T), RS1002733540 (7:93149362 C>T), RS1002809966 (7:93149939 C>T), RS1002831790 (7:93139214 G>A)

Disease associations

OMIM: gene MIM:611170 | disease phenotypes: MIM:159550, MIM:252270, MIM:619806, MIM:612650

GenCC curated gene-disease

Disease	Classification	Inheritance
ataxia-pancytopenia syndrome	Definitive	Autosomal dominant
SAMD9L-related spectrum and myeloid neoplasm risk	Definitive	Autosomal dominant
spinocerebellar ataxia 49	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
SAMD9L-related spectrum and myeloid neoplasm risk	Definitive	AD

Mondo (9): ataxia-pancytopenia syndrome (MONDO:0008038), monosomy 7 myelodysplasia and leukemia syndrome 1 (MONDO:0009646), spinocerebellar ataxia 49 (MONDO:0030805), primary ciliary dyskinesia 12 (MONDO:0012979), hereditary neoplastic syndrome (MONDO:0015356), SAMD9L-associated autoinflammatory syndrome (MONDO:0850066), microcephaly (MONDO:0001149), intellectual disability (MONDO:0001071), SAMD9L-related spectrum and myeloid neoplasm risk (MONDO:1060111)

Orphanet (6): Ataxia-pancytopenia syndrome (Orphanet:2585), Spinocerebellar ataxia type 49 (Orphanet:631106), Primary ciliary dyskinesia (Orphanet:244), Inherited cancer-predisposing syndrome (Orphanet:140162), SAMD9L-associated autoinflammatory syndrome (Orphanet:619367), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

48 total (30 of 48 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000486	Strabismus
HP:0000639	Nystagmus
HP:0000640	Gaze-evoked nystagmus
HP:0000651	Diplopia
HP:0000726	Dementia
HP:0000762	Decreased nerve conduction velocity
HP:0001251	Ataxia
HP:0001260	Dysarthria
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001310	Dysmetria
HP:0001347	Hyperreflexia
HP:0001744	Splenomegaly
HP:0001761	Pes cavus
HP:0001873	Thrombocytopenia
HP:0001874	Abnormality of neutrophils
HP:0001875	Decreased total neutrophil count
HP:0001876	Pancytopenia
HP:0001903	Anemia
HP:0001908	Hypoplastic anemia
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002075	Dysdiadochokinesis
HP:0002166	Impaired vibration sensation in the lower limbs
HP:0002167	Abnormal speech pattern
HP:0002205	Recurrent respiratory infections
HP:0002317	Unsteady gait
HP:0002500	Abnormal cerebral white matter morphology

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002069_6	Systemic lupus erythematosus and Systemic sclerosis	2.000000e-07
GCST007000_3	Logical memory (delayed recall) in mild cognitive impairment	3.000000e-09
GCST008314_1	Response to intravenous immunoglobulin treatment in Kawasaki disease	5.000000e-06
GCST009391_1145	Metabolite levels	6.000000e-06
GCST90026413_4	Severe insulin-deficient type 2 diabetes	3.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance
EFO:0010065	response to intravenous immunoglobulin therapy
EFO:0010457	Alpha ketoglutarate measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
C567211	Ciliary Dyskinesia, Primary, 12 (supp.)
C565370	Monosomy 7 of Bone Marrow (supp.)
C563233	Myelocerebellar Disorder (supp.)

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
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	4
bisphenol A	decreases expression, increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
(+)-JQ1 compound	decreases expression	2
Nickel	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Tretinoin	increases expression	2
Cyclosporine	increases expression	2
GSK-J4	decreases expression	1
sotorasib	affects cotreatment, increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
decabromobiphenyl ether	decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	affects expression	1
tetrabromobisphenol A	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
epigallocatechin gallate	increases expression, affects cotreatment, decreases expression	1
avobenzone	decreases expression	1
chromium hexavalent ion	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
MRK 003	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, increases expression	1
MT19c compound	increases expression	1

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1HF	Abcam A-549 SAMD9L KO 2	Cancer cell line	Male
CVCL_B2PY	Abcam A-549 SAMD9L KO 1	Cancer cell line	Male
CVCL_C0LU	GM28368	Finite cell line	Male
CVCL_E1EM	Ubigene U-87 MG SAMD9L KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT00001496	Not specified	COMPLETED	Establishment of Normal Breast Epithelial Cell Lines From Patients at High Risk for Breast Cancer
NCT00001898	Not specified	COMPLETED	Microarray Analysis for Human Genetic Disease
NCT00026884	Not specified	RECRUITING	Collection of Serum and Tissue Samples From Patients With Biopsy-Proved or Suspected Malignant Disease
NCT02289326	Not specified	COMPLETED	Biomarker Monitoring in TP53 Mutation Carriers
NCT02958462	Not specified	RECRUITING	Pre-myeloid Cancer and Bone Marrow Failure Clinic Study
NCT03160274	Not specified	RECRUITING	Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions
NCT03426878	Not specified	COMPLETED	Cancer Health Assessments Reaching Many
NCT03857594	Not specified	ACTIVE_NOT_RECRUITING	Integrative Sequencing In Germline and Hereditary Tumours
NCT03973450	Not specified	UNKNOWN	Epidemiology of Pituitary Tumours: Prevalence of Associated Neoplasia
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04261972	Not specified	ACTIVE_NOT_RECRUITING	Cell-free DNA in Hereditary And High-Risk Malignancies 1
NCT04494945	Not specified	RECRUITING	Identifying and Caring for Individuals With Inherited Cancer Syndrome
NCT04541654	Not specified	RECRUITING	Li-Fraumeni & TP53 (LiFT UP): Understanding and Progress
NCT04763915	Not specified	ACTIVE_NOT_RECRUITING	Improving Care After Inherited Cancer Testing
NCT05562778	Not specified	RECRUITING	Chatbot to Maximize Hereditary Cancer Genetic Risk Assessment
NCT05664867	Not specified	RECRUITING	Implementation of Population Cancer Genetic Services in Federally Qualified Health Centers (FQHC)
NCT05721326	Not specified	COMPLETED	Sequential EHR Based Interventions to Increase Genetic Testing for Breast and Ovarian Cancer Predisposition
NCT06096688	Not specified	RECRUITING	Discovering New Targets for Colorectal and Endometrial Cancer Risk Reduction
NCT06654466	Not specified	RECRUITING	Closing the GAPS: Guideline Adherence, Prevention and Surveillance in Hereditary Cancer
NCT06708429	Not specified	RECRUITING	Lynch Syndrome X-Talk of Enteral Mucosa With Immune System
NCT06726642	Not specified	RECRUITING	CfDNA in Hereditary And High-risk Malignancies 2
NCT06914726	Not specified	ENROLLING_BY_INVITATION	Patient Centered Clinical Decision Support for Hereditary Cancer Syndromes
NCT06927947	Not specified	RECRUITING	Navigation Interventions to Improve Cascade Genetic Testing Among Relatives of Patients With Hereditary Cancer Syndromes
NCT06999954	Not specified	RECRUITING	Shwachman-Diamond Syndrome Global Patient Survey and Partnering Platform
NCT07052266	Not specified	RECRUITING	Trial of Combined Obstetric Carrier Screening and Hereditary Cancer Screening
NCT07195071	Not specified	RECRUITING	Feasibility Trial of Combination of Obstetrical Carrier Screening and Hereditary Cancer Screening