STX16

Summary

STX16 (syntaxin 16, HGNC:11431) is a protein-coding gene on chromosome 20q13.32, encoding Syntaxin-16 (O14662). SNARE involved in vesicular transport from the late endosomes to the trans-Golgi network.

This gene encodes a protein that is a member of the syntaxin or t-SNARE (target-SNAP receptor) family. These proteins are found on cell membranes and serve as the targets for V-SNARES (vesicle-SNAP receptors) permitting specific synaptic vesicle docking and fusion. A microdeletion in the region of chromosome 20 where this gene is located has been associated with pseudohypoparathyroidism type Ib. Multiple transcript variants have been found for this gene. Read-through transcription also exists between this gene and the neighboring downstream aminopeptidase-like 1 (NPEPL1) gene.

Source: NCBI Gene 8675 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pseudohypoparathyroidism type 1B (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 291 total — 6 pathogenic
• Phenotypes (HPO): 44
• MANE Select transcript: NM_001001433

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11431
Approved symbol	STX16
Name	syntaxin 16
Location	20q13.32
Locus type	gene with protein product
Status	Approved
Aliases	hsyn16, SYN16, SYN-16
Ensembl gene	ENSG00000124222
Ensembl biotype	protein_coding
OMIM	603666
Entrez	8675

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 13 protein_coding, 6 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

ENST00000312283, ENST00000355957, ENST00000358029, ENST00000359617, ENST00000371132, ENST00000371141, ENST00000412911, ENST00000438253, ENST00000458280, ENST00000460655, ENST00000464640, ENST00000467096, ENST00000468590, ENST00000476384, ENST00000483434, ENST00000490700, ENST00000493301, ENST00000496003, ENST00000496117, ENST00000924625, ENST00000950354, ENST00000950355, ENST00000950356

RefSeq mRNA: 5 — MANE Select: NM_001001433 NM_001001433, NM_001134772, NM_001134773, NM_001204868, NM_003763

CCDS: CCDS13468, CCDS13469, CCDS46619, CCDS46620, CCDS56199

Canonical transcript exons

ENST00000371141 — 9 exons

Exon	Start	End
ENSE00001435967	58676187	58679526
ENSE00001866183	58651283	58652138
ENSE00003492144	58673631	58673711
ENSE00003502573	58670512	58670603
ENSE00003517224	58659623	58659634
ENSE00003526827	58671154	58671297
ENSE00003550444	58667490	58667597
ENSE00003635517	58669291	58669453
ENSE00003679389	58667987	58668127

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 97.69.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4204 / max 108.5483, expressed in 542 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185510	21.0266	1812
185511	1.4204	542

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.69	gold quality
sural nerve	UBERON:0015488	97.23	gold quality
corpus callosum	UBERON:0002336	97.03	gold quality
endometrium epithelium	UBERON:0004811	96.70	gold quality
superficial temporal artery	UBERON:0001614	96.66	gold quality
pituitary gland	UBERON:0000007	96.48	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.35	gold quality
cerebellar hemisphere	UBERON:0002245	96.24	gold quality
tibial nerve	UBERON:0001323	96.22	gold quality
cerebellar cortex	UBERON:0002129	96.20	gold quality
body of uterus	UBERON:0009853	96.18	gold quality
right ovary	UBERON:0002118	96.14	gold quality
adenohypophysis	UBERON:0002196	96.14	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.14	gold quality
left ovary	UBERON:0002119	96.13	gold quality
cerebellum	UBERON:0002037	95.93	gold quality
spinal cord	UBERON:0002240	95.93	gold quality
endocervix	UBERON:0000458	95.92	gold quality
inferior vagus X ganglion	UBERON:0005363	95.80	gold quality
granulocyte	CL:0000094	95.77	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.72	gold quality
lower esophagus	UBERON:0013473	95.71	gold quality
secondary oocyte	CL:0000655	95.67	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.67	gold quality
monocyte	CL:0000576	95.62	gold quality
stromal cell of endometrium	CL:0002255	95.60	gold quality
middle frontal gyrus	UBERON:0002702	95.59	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.54	gold quality
left uterine tube	UBERON:0001303	95.49	gold quality
subthalamic nucleus	UBERON:0001906	95.47	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6386	no	500.18
E-CURD-112	no	2.61
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

176 targeting STX16, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-12136	99.98	72.81	5713
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-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3148	99.97	75.06	6478

Literature-anchored findings (GeneRIF, showing 15)

• the region of overlap between the two microdeletions likely harbors a cis-acting imprinting control element that is necessary for establishing and methylation at GNAS exon A/B, thus allowing normal G alpha(s) expression in the proximal renal tubules. I (PMID:15800843)
• function of syntaxin 16 was specifically required for, and restricted to, the retrograde pathway (PMID:17389686)
• Syntaxin 16 may thus play a role in neurite outgrowth and perhaps other specific dendritic anterograde/retrograde traffic. (PMID:17852734)
• phosphorylation of RASSF1A by Aurora B is required for the recruitment of Syntaxin16 (PMID:19887622)
• Results suggest that STX16 mediates recycling of CFTR and constitutes an important component of CFTR trafficking machinery in intestinal epithelial cells. (PMID:20826815)
• De novo 3-kb STX16 deletions, reported only once previously, are infrequent but should be excluded in all cases of Pseudohypoparathyroidism-Ib, even when the family history is negative for an inherited form of this disorder. (PMID:23087324)
• A patient with familial pseudohypoparathyroidism type Ib and his asymptomatic brother were found to have methylation defect at GNAS (guanine nucleotide-binding protein G) and microdeletion involving exons 4-6 of neighboring gene STX16. [CASE REPORT] (PMID:23095209)
• Data indicate that depletion of VAMP4, syntaxin 6, syntaxin 16, and Vti1a disrupted the Golgi ribbon structure. (PMID:23677696)
• syntaxin 16 is a key regulator of cytokinesis. (PMID:24109596)
• STX16 microdeletion was identified in male monozygotic twins (with pseudohypoparathyroidism type 1B leading to growth hormone deficiency) and mother/grandmother (not father/grandfather or sister [their triplet with separate placenta]). [CASE STUDY] (PMID:25843330)
• we here present a patient with PHP1b caused by a recurrent STX16 deletion, presenting with macrosomia, early onset obesity, and macrocephaly without other AHO symptoms. we reemphasize STX16 deletions and PHP1b as a rare cause for early onset obesity and macrosomia. (PMID:27338644)
• Preferential Maternal Transmission of STX16-GNAS Mutations Responsible for Autosomal Dominant Pseudohypoparathyroidism Type Ib (PHP1B): Another Example of Transmission Ratio Distortion. (PMID:33247854)
• Analysis of defects in GNAS and STX16 genes in a Chinese family with pseudohypoparathyroidism. (PMID:33269569)
• Progression of PTH Resistance in Autosomal Dominant Pseudohypoparathyroidism Type Ib Due to Maternal STX16 Deletions. (PMID:34477200)
• Intrafamilial phenotypic heterogeneity in siblings with pseudohypoparathyroidism 1B due to maternal STX16 deletion. (PMID:38095637)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	stx16	ENSDARG00000003307
mus_musculus	Stx16	ENSMUSG00000027522
rattus_norvegicus	Stx16	ENSRNOG00000005281
drosophila_melanogaster	Syx16	FBGN0031106
caenorhabditis_elegans		WBGENE00022534

Paralogs (12): STX7 (ENSG00000079950), STX1B (ENSG00000099365), STX4 (ENSG00000103496), STX1A (ENSG00000106089), STX2 (ENSG00000111450), STX12 (ENSG00000117758), STX11 (ENSG00000135604), STX17 (ENSG00000136874), STX5 (ENSG00000162236), STX3 (ENSG00000166900), TSNARE1 (ENSG00000171045), STX19 (ENSG00000178750)

Protein

Protein identifiers

Syntaxin-16 — O14662 (reviewed: O14662)

All UniProt accessions (9): B7ZBM4, B7ZBM5, B7ZBM8, E9PLV7, E9PND6, F8W9Z6, H0YEW0, O14662, Q96NX8

UniProt curated annotations — full annotation on UniProt →

Function. SNARE involved in vesicular transport from the late endosomes to the trans-Golgi network.

Subunit / interactions. Interacts with GCC2. Interacts with BAIAP3; this interaction is increased in the presence of calcium.

Subcellular location. Golgi apparatus membrane Cytoplasm.

Tissue specificity. Ubiquitous.

Disease relevance. Pseudohypoparathyroidism 1B (PHP1B) [MIM:603233] A disorder characterized by end-organ resistance to parathyroid hormone, hypocalcemia and hyperphosphatemia. Patients affected with PHP1B lack developmental defects characteristic of Albright hereditary osteodystrophy, and typically show no other endocrine abnormalities besides resistance to PTH. The gene represented in this entry is involved in disease pathogenesis. Microdeletions involving STX16 can cause loss of methylation at exon A/B of GNAS, resulting in PHP1B.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the syntaxin family.

Isoforms (6)

UniProt ID	Names	Canonical?
O14662-1	B	yes
O14662-2	A
O14662-3	C
O14662-4	D
O14662-5	E
O14662-6	6

RefSeq proteins (5): NP_001001433, NP_001128244, NP_001128245, NP_001191797, NP_003754 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000727	T_SNARE_dom	Domain
IPR006012	Syntaxin/epimorphin_CS	Conserved_site
IPR010989	SNARE	Homologous_superfamily
IPR045242	Syntaxin	Family

Pfam: PF05739

UniProt features (15 total): splice variant 6, sequence conflict 3, topological domain 2, chain 1, transmembrane region 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8QQF	X-RAY DIFFRACTION	2.19

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14662-F1	76.87	0.27

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 (1): 41

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-6811438	Intra-Golgi traffic
R-HSA-6811440	Retrograde transport at the Trans-Golgi-Network
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic

MSigDB gene sets: 425 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, AAGCAAT_MIR137, MORF_MBD4, MORF_RAB5A, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_VESICLE_ORGANIZATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_MEMBRANE_FUSION, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (7): intracellular protein transport (GO:0006886), vesicle fusion (GO:0006906), endocytic recycling (GO:0032456), retrograde transport, endosome to Golgi (GO:0042147), obsolete vesicle docking (GO:0048278), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192)

GO Molecular Function (4): SNARE binding (GO:0000149), SNAP receptor activity (GO:0005484), syntaxin binding (GO:0019905), protein binding (GO:0005515)

GO Cellular Component (15): Golgi membrane (GO:0000139), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), trans-Golgi network (GO:0005802), cytosol (GO:0005829), focal adhesion (GO:0005925), endomembrane system (GO:0012505), membrane (GO:0016020), synaptic vesicle membrane (GO:0030672), SNARE complex (GO:0031201), Golgi cisterna (GO:0031985), trans-Golgi network membrane (GO:0032588), intracellular membrane-bounded organelle (GO:0043231), perinuclear region of cytoplasm (GO:0048471), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Intra-Golgi and retrograde Golgi-to-ER traffic	2
Vesicle-mediated transport	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	5
intracellular protein localization	2
endosomal transport	2
transport	2
intracellular anatomical structure	2
endomembrane system	2
intracellular membrane-bounded organelle	2
Golgi apparatus subcompartment	2
protein transport	1
intracellular transport	1
vesicle organization	1
vesicle-mediated transport	1
organelle membrane fusion	1
vesicle-mediated transport to the plasma membrane	1
intercellular transport	1
cytosolic transport	1
establishment of protein localization	1
cellular process	1
protein binding	1
protein-macromolecule adaptor activity	1
membrane fusion	1
fusogenic activity	1
SNARE binding	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
cell-substrate junction	1
vacuole	1
plasma membrane	1
synaptic vesicle	1
exocytic vesicle membrane	1
membrane protein complex	1
Golgi stack	1
trans-Golgi network	1
organelle membrane	1
membrane-bounded organelle	1
intracellular organelle	1

Protein interactions and networks

STRING

1614 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STX16	STX6	O43752	996
STX16	VTI1A	Q96AJ9	996
STX16	VAMP4	O75379	991
STX16	STX10	O60499	986
STX16	VAMP3	Q15836	983
STX16	GCC2	Q8IWJ2	957
STX16	VPS45	Q9NRW7	937
STX16	VPS53	Q5VIR6	903
STX16	GNAS	Q5JWF2	870
STX16	VPS54	Q9P1Q0	857
STX16	VAMP7	P51809	819
STX16	COG8	Q96MW5	819
STX16	VTI1B	Q9UEU0	819
STX16	PTH	P01270	814
STX16	STX8	Q9UNK0	813

IntAct

59 interactions, top by confidence:

A	B	Type	Score
STX16	VAMP5	psi-mi:“MI:0915”(physical association)	0.740
VAMP5	STX16	psi-mi:“MI:0915”(physical association)	0.740
STX12	SNAP23	psi-mi:“MI:0914”(association)	0.640
VPS45	STX16	psi-mi:“MI:0915”(physical association)	0.620
VPS45	STX16	psi-mi:“MI:0914”(association)	0.620
MEOX2	STX16	psi-mi:“MI:0915”(physical association)	0.560
STX4	STX16	psi-mi:“MI:0915”(physical association)	0.560
NAPB	STX16	psi-mi:“MI:0915”(physical association)	0.560
STX16	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
NAPA	NBAS	psi-mi:“MI:0914”(association)	0.530
GDPD5	GOLIM4	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
VAMP5	NBAS	psi-mi:“MI:0914”(association)	0.530
ANKH	FAM234B	psi-mi:“MI:0914”(association)	0.530
SPDEF	STX16	psi-mi:“MI:0915”(physical association)	0.400
STX16	H2BC12L	psi-mi:“MI:0915”(physical association)	0.400
STX16	PTPN12	psi-mi:“MI:0915”(physical association)	0.370
VPS50	STX16	psi-mi:“MI:0914”(association)	0.350
OCRL	MYO1C	psi-mi:“MI:0914”(association)	0.350
VAMP5	ESYT2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (120): STX16 (Two-hybrid), STX16 (Two-hybrid), VAMP5 (Two-hybrid), NAPB (Two-hybrid), STX16 (Two-hybrid), STX16 (Affinity Capture-Western), ATP6V1B2 (Co-fractionation), STX16 (Co-fractionation), STX16 (Proximity Label-MS), STX16 (Reconstituted Complex), STX16 (Proximity Label-MS), STX16 (Affinity Capture-MS), STX16 (Affinity Capture-MS), STX16 (Affinity Capture-MS), STX16 (Affinity Capture-MS)

ESM2 similar proteins: G3V7P1, O08522, O14662, O15400, O22151, O43752, O49377, O60499, O64791, O70257, O70439, O70480, O75379, O88384, O88630, O88983, O95249, P58200, Q08851, Q08DB5, Q13190, Q2KIU0, Q2TBU3, Q32L97, Q3T075, Q3ZBT5, Q5R602, Q5R6Q2, Q5RBL6, Q5RBW6, Q5RF94, Q5SRX1, Q5ZL19, Q62931, Q63635, Q86Y82, Q8BVI5, Q8K1E0, Q944A9, Q946Y7

Diamond homologs: A8WVD0, G3V7P1, O14662, O15400, O16000, O35526, O64791, O65359, O70257, O70439, O94651, P32850, P32851, P32854, P32856, P50279, P61264, P61265, P61266, P61267, P61268, P70452, P91409, Q00262, Q08144, Q08849, Q08850, Q12846, Q13277, Q16623, Q16932, Q24547, Q3SWZ3, Q3ZBT5, Q42374, Q54JY7, Q54X86, Q5R4L2, Q5R602, Q5RBW6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
STX16	“form complex”	“LE-TGN SNARE”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 54 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Intra-Golgi traffic	8	57.7×	1e-10
Retrograde transport at the Trans-Golgi-Network	7	42.7×	9e-09
Intra-Golgi and retrograde Golgi-to-ER traffic	8	23.3×	5e-08
Membrane Trafficking	12	12.4×	7e-09
Vesicle-mediated transport	12	11.6×	9e-09

GO biological processes:

GO term	Partners	Fold	FDR
intracellular protein transport	9	12.4×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	0
Uncertain significance	168
Likely benign	33
Benign	72

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
2423450	NC_000020.10:g.(?57244327)(57246373_?)del	Pathogenic
3901267	NC_000020.10:g.55906911_58646228del	Pathogenic
4277543	NM_001001433.3(STX16):c.556+1G>A	Pathogenic
6149	NM_001001433.3(STX16):c.145-2060_556+343del	Pathogenic
625617	GRCh37/hg19 20q13.32(chr20:57244540-57246216)	Pathogenic
978043	NM_001001433.3(STX16):c.393+557_792+364del	Pathogenic

SpliceAI

1919 predictions. Top by Δscore:

Variant	Effect	Δscore
20:58651401:G:GT	donor_gain	1.0000
20:58651402:A:T	donor_gain	1.0000
20:58651412:G:GT	donor_gain	1.0000
20:58652046:C:CA	acceptor_gain	1.0000
20:58659560:ATGCT:A	acceptor_gain	1.0000
20:58659561:T:G	acceptor_gain	1.0000
20:58659564:T:A	acceptor_gain	1.0000
20:58667485:TGTA:T	acceptor_loss	1.0000
20:58667487:TA:T	acceptor_loss	1.0000
20:58667487:TAGCT:T	acceptor_loss	1.0000
20:58667488:A:AG	acceptor_gain	1.0000
20:58667488:AG:A	acceptor_loss	1.0000
20:58667489:G:GG	acceptor_gain	1.0000
20:58667489:GCTT:G	acceptor_gain	1.0000
20:58667595:GAA:G	donor_gain	1.0000
20:58667597:AG:A	donor_loss	1.0000
20:58667598:G:GG	donor_gain	1.0000
20:58667599:TAA:T	donor_loss	1.0000
20:58669290:GC:G	acceptor_gain	1.0000
20:58669451:AAC:A	donor_gain	1.0000
20:58669452:AC:A	donor_gain	1.0000
20:58669453:CG:C	donor_loss	1.0000
20:58669454:G:GC	donor_loss	1.0000
20:58669454:G:GG	donor_gain	1.0000
20:58669454:G:T	donor_loss	1.0000
20:58669457:AGTGC:A	donor_loss	1.0000
20:58670507:GATA:G	acceptor_loss	1.0000
20:58670507:GATAG:G	acceptor_loss	1.0000
20:58670508:ATAGG:A	acceptor_loss	1.0000
20:58670509:TA:T	acceptor_loss	1.0000

AlphaMissense

2133 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:58673704:T:C	L289P	0.998
20:58676187:G:C	A292P	0.997
20:58671254:T:C	L250P	0.996
20:58673650:T:A	I271N	0.996
20:58673662:T:A	V275D	0.996
20:58667577:T:A	W78R	0.995
20:58667577:T:C	W78R	0.995
20:58671212:G:C	R236P	0.995
20:58671241:T:C	S246P	0.995
20:58669403:T:C	L169P	0.994
20:58673631:G:C	G265R	0.994
20:58673641:T:A	L268H	0.994
20:58673650:T:G	I271S	0.994
20:58673670:T:C	S278P	0.994
20:58673691:G:C	G285R	0.993
20:58673692:G:A	G285D	0.993
20:58652017:G:T	R4M	0.992
20:58652034:T:C	F10L	0.992
20:58652036:C:A	F10L	0.992
20:58652036:C:G	F10L	0.992
20:58669427:G:C	R177P	0.992
20:58673704:T:A	L289H	0.992
20:58673641:T:C	L268P	0.991
20:58652047:G:C	R14P	0.990
20:58671265:T:C	F254L	0.990
20:58671267:C:A	F254L	0.990
20:58671267:C:G	F254L	0.990
20:58669448:T:C	L184P	0.989
20:58671263:T:A	I253K	0.988
20:58673643:G:C	D269H	0.988

dbSNP variants (sampled 300 via entrez): RS1000025915 (20:58661518 G>A), RS1000108948 (20:58678345 T>C), RS1000299116 (20:58650951 C>A), RS1000349265 (20:58664634 A>G), RS1000452002 (20:58657472 C>A,G), RS1000479237 (20:58670005 G>A), RS1000830776 (20:58652237 T>C,G), RS1000888510 (20:58653079 G>A), RS1000903734 (20:58672657 T>C), RS1000980335 (20:58657774 T>G), RS1001064731 (20:58665329 A>C), RS1001091241 (20:58663173 C>G), RS1001095144 (20:58669646 G>A), RS1001203316 (20:58672833 G>A), RS1001235743 (20:58678604 C>T)

Disease associations

OMIM: gene MIM:603666 | disease phenotypes: MIM:603233, MIM:612462

GenCC curated gene-disease

Disease	Classification	Inheritance
pseudohypoparathyroidism type 1B	Strong	Autosomal dominant

Mondo (2): pseudohypoparathyroidism type 1B (MONDO:0011301), pseudohypoparathyroidism type 1C (MONDO:0012911)

Orphanet (2): Pseudohypoparathyroidism type 1B (Orphanet:94089), Pseudohypoparathyroidism type 1C (Orphanet:79444)

HPO phenotypes

44 total (30 of 44 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000293	Full cheeks
HP:0000311	Round face
HP:0000470	Short neck
HP:0000509	Conjunctivitis
HP:0000518	Cataract
HP:0000639	Nystagmus
HP:0000684	Delayed eruption of teeth
HP:0000716	Depression
HP:0000737	Irritability
HP:0000739	Anxiety
HP:0000824	Decreased response to growth hormone stimulation test
HP:0000852	Pseudohypoparathyroidism
HP:0001156	Brachydactyly
HP:0001265	Hyporeflexia
HP:0001513	Obesity
HP:0001657	Prolonged QT interval
HP:0002094	Dyspnea
HP:0002199	Hypocalcemic seizures
HP:0002901	Hypocalcemia
HP:0002905	Hyperphosphatemia
HP:0003034	Diaphyseal sclerosis
HP:0003165	Elevated circulating parathyroid hormone level
HP:0003394	Muscle spasm
HP:0003401	Paresthesia
HP:0003456	Low urinary cyclic AMP response to PTH administration
HP:0003472	Hypocalcemic tetany
HP:0003739	Myoclonic spasms
HP:0003745	Sporadic
HP:0003761	Calcinosis

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000789_2	Cardiovascular risk factors (age interaction)	1.000000e-06
GCST90002384_477	Hemoglobin	1.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0008007	age at assessment
EFO:0004509	hemoglobin measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C548076	Pseudohypoparathyroidism Type 1C (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases expression, affects expression, decreases expression, affects cotreatment, increases abundance	4
sodium arsenite	decreases expression, increases abundance, increases expression	3
Valproic Acid	affects expression, increases expression	3
methylmercuric chloride	affects cotreatment, increases expression	2
Ozone	affects cotreatment, increases expression, increases abundance, affects expression	2
Tretinoin	increases expression, decreases expression	2
Cyclosporine	increases expression	2
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
cobaltous chloride	increases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	increases expression, increases abundance, affects cotreatment	1
tamibarotene	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Atrazine	increases expression	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03718403	PHASE4	RECRUITING	Effect of Theophylline in Pseudohypoparathyroidism